Breastfeeding and Children’s Cognitive Development up to the Age of 4 Years: The Japan Environment and Children’s Study

Abstract

Objective:

Breastfeeding, depending on its duration, has been suggested to benefit children’s cognitive development. We aimed to examine this issue by using the Japan Environment and Children’s Study, a nationwide prospective birth cohort study.

Methods:

We evaluated the relationship between feeding methods and cognitive development in 2- and 4-year-old children. We classified the children based on the following feeding method during the first 6 months postpartum: (1) exclusive breastfeeding group, solely breastfeeding; (2) partial breastfeeding group, solely breastfeeding for ≤5 months and combination of breastfeeding/formula for the rest of months; (3) formula-fed group, solely formula feeding for ≥4 months; and (4) others. Cognitive development was assessed by trained testers using the Kyoto Scale of Psychological Development 2001.

Results:

Data on 1,329 boys and 1,398 girls were analyzed. Multiple regression analysis was performed using the exclusive breastfeeding group as the reference. Boys of age 2 years in the formula-fed group had significantly lower developmental quotients (DQs) in the language-social developmental (L-S) area (partial regression coefficient [B]: −4.624, p = 0.01), whereas no significant difference was observed in those of age 4 years. Girls of age 2 and 4 years in the formula-fed group had significantly lower L-S area DQ (B: −3.637, p = 0.03 and B: −3.414, p = 0.03, respectively). In the partial breastfeeding group, no significant differences in the L-S area DQ were observed in 2- and 4-year-old boys and girls.

Conclusions:

Exclusive breastfeeding for the first 6 months postpartum may be more beneficial for verbal cognitive development in 4-year-old girls than solely formula feeding for ≥4 months. Furthermore, breastfeeding combined with formula for the first 6 months postpartum may not have a disadvantage on cognitive development in boys and girls of age ≥ 2 years, when compared with that observed with exclusive breastfeeding during the first 6 months postpartum.

Introduction

According to evidence-based meta-analyses and systematic reviews, the World Health Organization recommends exclusive breastfeeding for longer than the first 6 months.^1–3 Depending on its duration, breastfeeding, especially exclusive breastfeeding, has been suggested to benefit children’s cognitive development.^4–7 However, the data on which this notion is based did not include Japanese studies. Furthermore, it has been suggested that the benefits of breastfeeding vary by country, including differences between developing and developed countries.^2,6,7

In the present study, we used the Japan Environment and Children’s Study (JECS) to examine whether exclusive breastfeeding for the first 6 months benefits children’s cognitive development more than other feeding methods in Japan.^8,9 The JECS is a nationwide prospective birth cohort study in which children’s cognitive development was objectively assessed by trained testers in the Sub-Cohort Study.¹⁰ Previous foreign studies reported that the benefits of breastfeeding varied according to the trajectories of children’s age. However, few studies have examined the sexes separately. Therefore, this study evaluated 2- and 4-year-old children and sexes separately.

Materials and Methods

Design and participants

The JECS protocol was conducted in accordance with the guidelines of the Declaration of Helsinki. The study was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (No. 100910001) and the Ethics Committees of all the participating institutions. JECS recruitment occurred between January 2011 and March 2014 and included pregnant women nationwide.^8,9 Participants were recruited from 15 Regional Centers located in Hokkaido, Miyagi, Fukushima, Chiba, Kanagawa, Koshin, Toyama, Aichi, Kyoto, Osaka, Hyogo, Tottori, Kochi, Fukuoka, and South Kyushu/Okinawa. Written informed consent was obtained from all the participants. Participants of the Sub-Cohort Study, comprising 5% of the participating children who were randomly selected and met the eligibility criteria, were extracted from the JECS.¹⁰ For this Sub-Cohort Study, extended outcome measurements were planned, comprising face-to-face interviews with specialized staff to evaluate neurological development based on the Kyoto Scale of Psychological Development 2001 (KSPD) for 2- and 4-year-old children.^11–16

The present study used the jecs-ta-20190930 ver008 and the jecs-qa-20210401 ver005 datasets. The datasets contain the cognitive developmental results of 2- and 4-year-old children based on the KSPD. Data from 2- and 4-year-old children were matched to compare relative changes. Considering this study included children from singleton pregnancies, multiple-birth children were excluded. Preterm-born children (delivered at <37 weeks of pregnancy) and those with any congenital anomalies were also excluded.¹⁷ Only children who met the requirements of this study at ages 2 and 4 years were included.

Feeding method

Self-administered questionnaires were used to estimate the maternal feeding method for children at approximately the first 6 months postpartum.

We classified participants into four groups based on feeding method during the first 6 months postpartum: (1) exclusive breastfeeding group, solely breastfeeding for 6 months; (2) partial breastfeeding group, solely breastfeeding for ≤5 months and combination of breastfeeding and formula for the rest of months, including combination of breastfeeding and formula for 6 months; (3) formula-fed group, solely formula feeding for ≥4 months—this group includes the following cases: solely formula feeding for 6 months or either solely breastfeeding or combining breastfeeding and formula for the first 1 or 2 months postpartum and solely formula for the later months; and (4) other group, participants who did not meet the conditions mentioned in the aforementioned three groups (Tables 1 and 2).

Table 1.

The Characteristics of Participants (Total = 2,727)

	Overall (n = 2,727)		Boys (n = 1,329)		Girls (n = 1,398)		Reference for multiple regression analysis
	n	%	n	%	n	%	Reference for multiple regression analysis
Maternal age at delivery
Means ± SD	32.1 ± 4.8		32.2 ± 4.7		32.0 ± 4.9		Continuous variable
<20	4	0.2	3	0.2	1	0.1
20–24	158	5.8	68	5.1	90	6.4
25–34	1,673	61.4	817	61.5	856	61.2
≥35	892	32.7	441	33.2	451	32.3
Parity
Primipara	1,079	39.6	528	39.7	551	39.4
Multipara	1,606	58.9	781	58.8	825	59.0
No answer	42	1.5	20	1.5	22	1.6
Unplanned pregnancy
No	2,535	93.0	1,231	92.6	1,304	93.3	Ref
Yes	192	7.0	98	7.4	94	6.7
No answer
Infertility treatment
No	2,525	92.6	1,229	92.5	1,296	92.7	Ref
Yes	202	7.4	100	7.5	102	7.3
Marital status
Married, Common-law marriage	2,696	98.9	1,315	99.0	1,381	98.8	Ref
Divorce, lost, other	31	1.1	14	1.1	17	1.2
Maternal academic history (year)
≤12	824	30.2	375	28.2	449	32.1
13–15	1,140	41.8	575	43.3	565	40.4
≥16	763	28.0	379	28.5	384	27.5	Ref
Paternal academic history (year)
≤12	998	36.6	470	35.4	528	37.8
13–15	605	22.2	286	21.5	319	22.8
≥16	1,124	41.2	573	43.1	551	39.4	Ref
Maternal smoking during pregnancy
No	2,658	97.5	1,296	97.5	1,362	97.4	Ref
Yes	69	2.5	33	2.5	36	2.6
Paternal smoking during pregnancy
No	1,682	61.7	832	62.6	850	60.8	Ref
Yes	1,045	38.3	497	37.4	548	39.2
Maternal alcohol consumption during pregnancy
No	2,661	97.6	1,293	97.3	1,368	97.9	Ref
Yes	66	2.4	36	2.7	30	2.2
Household income (×10³ yen/year) during pregnancy
<4,000	987	36.2	463	34.8	524	37.5	Ref
4,000≤ to <6,000	930	34.1	471	35.4	459	32.8
≥6,000	810	29.7	395	29.7	415	29.7
Maternal neuropsychiatric disorders
No	2,465	90.4	1,201	90.4	1,264	90.4	Ref
Yes	262	9.6	128	9.6	134	9.6
Psychoactive drugs use during pregnancy
No	2,661	97.6	1,300	97.8	1,361	97.4	Ref
Yes	66	2.4	29	2.2	37	2.7
Phycological IPV during pregnancy
No	2,403	88.1	1,171	88.1	1,232	88.1	Ref
Yes	324	11.9	158	11.9	166	11.9
Physical IPV during pregnancy
No	2,705	99.2	1,318	99.2	1,387	99.2	Ref
Yes	22	0.8	11	0.8	11	0.8
Maternal depression (EPDS ≥9) at postpartum 6 months
No	2,480	90.9	1,214	91.4	1,266	90.6	Ref
Yes	247	9.1	115	8.7	132	9.4
Maternal bonding failure (MIBS ≥5) at postpartum 1 year
No	2,446	89.7	1,172	88.2	1,274	91.1	Ref
Yes	281	10.3	157	11.8	124	8.9
Pregnancy complication
No	2,304	84.5	1,120	84.3	1,184	84.7	Ref
Yes	423	15.5	209	15.7	214	15.3
Obstetric labor complication
No	1,509	55.3	733	55.2	776	55.5	Ref
Yes	1,218	44.7	596	44.9	622	44.5
Delivery mode
Vaginal	2,296	84.2	1,128	84.9	1,168	83.6	Ref
Cesarean	431	15.8	201	15.1	230	16.5
Sex of children
Boy	1,329	48.7	1,329	100.0	0	0.0	Ref
Girl	1,398	51.3	0	0.0	1,398	100.0
Birth weight of children
Means ± SD	3,077.9 ± 371.3		3,131.7 ± 380.5		3,026.7 ± 355.1		Continuous variable
1,500≤ to <2,500	135	5.0	47	3.5	88	6.3
2,500≤ to <4,000	2,564	94.0	1,261	94.9	1,303	93.2
≥4,000	28	1.0	21	1.6	7	0.5
Family structure at age 1.5 years
Extended family	528	19.4	266	20.0	262	18.7
Nuclear family	2,199	80.6	1,063	80.0	1,136	81.3	Ref
Number of children at age 1.5 years including participants
1	1,096	40.2	542	40.8	554	39.6	Ref
2	1,090	40.0	528	39.7	562	40.2
≥3	541	19.8	259	19.5	282	20.2
Attendance age of daycare center at age 2 years
No	1,397	51.2	674	50.7	723	51.7	Ref
Yes; 0≤ to <1	618	22.7	307	23.1	311	22.3
Yes; 1≤	712	26.1	348	26.2	364	26.0
Attendance age of daycare center at age 4 years
Not attend	147	5.4	59	4.4	88	6.3
0≤ to <1	590	21.6	286	21.5	304	21.8
1≤ to <2	612	22.4	296	22.3	316	22.6
2≤ to <3	339	12.4	174	13.1	165	11.8
≥3	1,039	38.1	514	38.7	525	37.6	Ref
Regional Center
Hokkaido	206	7.6	95	7.2	111	7.9
Miyagi	253	9.3	133	10.0	120	8.6
Fukushima	334	12.3	169	12.7	165	11.8	Ref
Chiba	165	6.1	70	5.3	95	6.8
Kanagawa	164	6.0	78	5.9	86	6.2
Koshin	200	7.3	99	7.5	101	7.2
Toyama	143	5.2	73	5.5	70	5.0
Aichi	181	6.6	83	6.3	98	7.0
Kyoto	100	3.7	48	3.6	52	3.7
Osaka	190	7.0	87	6.6	103	7.4
Hyogo	147	5.4	86	6.5	61	4.4
Tottori	83	3.0	38	2.9	45	3.2
Kochi	181	6.6	85	6.4	96	6.9
Fukuoka	208	7.6	102	7.7	106	7.6
South Kyusyu and Okinawa	172	6.3	83	6.3	89	6.4
Exposure
1st month postpartum
Breastfeeding	1,565	57.4	750	56.4	815	58.3
Breastfeeding and formula-fed	1,107	40.6	554	41.7	553	39.6
Formula-fed	55	2.0	25	1.9	30	2.2
2nd month postpartum
Breastfeeding	1,707	62.6	828	62.3	879	62.9
Breastfeeding and formula-fed	902	33.1	445	33.5	457	32.7
Formula-fed	118	4.3	56	4.2	62	4.4
3rd month postpartum
Breastfeeding	1,787	65.5	870	65.5	917	65.6
Breastfeeding and formula-fed	758	27.8	377	28.4	381	27.3
Formula-fed	182	6.7	82	6.2	100	7.2
4th month postpartum
Breastfeeding	1,771	64.9	853	64.2	918	65.7
Breastfeeding and formula-fed	696	25.5	349	26.3	347	24.8
Formula-fed	260	9.5	127	9.6	133	9.5
5th month postpartum
Breastfeeding	1,709	62.7	828	62.3	881	63.0
Breastfeeding and formula-fed	699	25.6	347	26.1	352	25.2
Formula-fed	319	11.7	154	11.6	165	11.8
6th month postpartum
Breastfeeding	1,709	62.7	838	63.1	871	62.3
Breastfeeding and formula-fed	659	24.2	317	23.9	342	24.5
Formula-fed	359	13.2	174	13.1	185	13.2
Frequency of breastfeeding (max = 6 months)
0 month	42	1.5	21	1.6	21	1.5
1 month	70	2.6	33	2.5	37	2.7
2 months	67	2.5	27	2.0	40	2.9
3 months	84	3.1	46	3.5	38	2.7
4 months	58	2.1	26	2.0	32	2.3
5 months	55	2.0	29	2.2	26	1.9
6 months	2,351	86.2	1,147	86.3	1,204	86.1
Frequency of formula-fed (max = 6 months)
0 month	1,240	45.5	599	45.1	641	45.9
1 month	254	9.3	126	9.5	128	9.2
2 months	203	7.4	97	7.3	106	7.6
3 months	145	5.3	72	5.4	73	5.2
4 months	91	3.3	43	3.2	48	3.4
5 months	109	4.0	53	4.0	56	4.0
6 months	685	25.1	339	25.5	346	24.8
Feeding method during the first 6 months postpartum
Exclusive breastfeeding group	1,240	45.5	599	45.1	641	45.9	Ref
Partial breastfeeding group	1,111	40.7	548	41.2	563	40.3
Formula-fed group	179	6.6	81	6.1	98	7.0
Other group	197	7.2	101	7.6	96	6.9
Outcome
C-A DQ of KSPD at age 2 years
Means ± SD	96.4 ± 12.4		94.3 ± 11.7		98.4 ± 12.7
Minimum	47		58		47
25 percentiles	88		87		90
50 percentiles	95		93		97
75 percentiles	104		101		107
Maximum	145		133		145
L-S DQ of KSPD at age 2 years
Means ± SD	93.6 ± 14.8		90.7 ± 14.5		96.4 ± 14.6
Minimum	46		46		48
25 percentiles	84		81		87
50 percentiles	93		91		95
75 percentiles	102		99		106
Maximum	147		147		145
C-A DQ of KSPD at age 4 years
Means ± SD	96.7 ± 14.1		95.5 ± 14.7		97.8 ± 13.5
Minimum	24		44		24
25 percentiles	86		85		87
50 percentiles	97		95		99
75 percentiles	105		105		106
Maximum	153		153		152
L-S DQ of KSPD at age 4 years
Means ± SD	96.7 ± 15.4		96.3 ± 16.0		98.0 ± 14.7
Minimum	28		28		36
25 percentiles	85		84		88
50 percentiles	98		95		99
75 percentiles	107		106		107
Maximum	144		140		144

Exclusive breastfeeding group: solely breastfeeding for 6 months. Partial breastfeeding group: solely breastfeeding for ≤5 months and combination of breastfeeding and formula for the rest of months. Formula-fed group: solely formula feeding for ≥4 months. Other group: participants who did not meet the conditions mentioned in the aforementioned three groups.

SD, standard deviation; IPV, intimate partner violence; EPDS, Edinburgh Postnatal Depression Scale; MIBS, Mother–Infant Bonding Scale; KSPD, Kyoto scale of psychological development 2001; C-A, cognitive-adaptive; L-S, language-social; DQ, developmental quotient.

Table 2.

Feeding Method Status Detail During the First 6 Months Postpartum (Total = 2,727)

	Postpartum months
	1st	2nd	3rd	4th	5th	6th	n	%	%
Exclusive breastfeeding group	b	b	b	b	b	b	1,240	45.5	45.5
Partial breastfeeding group	b	b	b	b	b	b&f	18	0.7	40.7
	b	b	b	b	b&f	b	7	0.3
	b	b	b	b	b&f	b&f	46	1.7
	b	b	b	b&f	b	b	2	0.1
	b	b	b	b&f	b	b&f	1	0.0
	b	b	b	b&f	b&f	b	5	0.2
	b	b	b	b&f	b&f	b&f	45	1.7
	b	b	b&f	b&f	b	b	1	0.0
	b	b	b&f	b&f	b&f	b&f	41	1.5
	b	b&f	b	b	b	b	5	0.2
	b	b&f	b	b	b&f	b	1	0.0
	b	b&f	b	b&f	b	b	1	0.0
	b	b&f	b	b&f	b&f	b&f	1	0.0
	b	b&f	b&f	b	b	b	3	0.1
	b	b&f	b&f	b&f	b	b	1	0.0
	b	b&f	b&f	b&f	b&f	b&f	44	1.6
	b&f	b	b	b	b	b	217	8.0
	b&f	b	b	b	b	b&f	3	0.1
	b&f	b	b	b	b&f	b	3	0.1
	b&f	b	b	b	b&f	b&f	9	0.3
	b&f	b	b	b&f	b&f	b	1	0.0
	b&f	b	b	b&f	b&f	b&f	2	0.1
	b&f	b	b&f	b&f	b&f	b&f	4	0.1
	b&f	b&f	b	b	b	b	127	4.7
	b&f	b&f	b	b	b	b&f	1	0.0
	b&f	b&f	b	b	b&f	b	2	0.1
	b&f	b&f	b	b	b&f	b&f	5	0.2
	b&f	b&f	b	b&f	b&f	b&f	4	0.1
	b&f	b&f	b&f	b	b	b	59	2.2
	b&f	b&f	b&f	b	b&f	b&f	1	0.0
	b&f	b&f	b&f	b&f	b	b	17	0.6
	b&f	b&f	b&f	b&f	b&f	b	7	0.3
	b&f	b&f	b&f	b&f	b&f	b&f	427	15.7
Formula-fed group	b	b	f	f	f	f	7	0.3	6.6
	b	b&f	f	f	f	f	9	0.3
	b&f	b&f	f	f	f	f	51	1.9
	b	f	f	f	f	f	19	0.7
	b&f	f	f	f	f	f	51	1.9
	f	f	f	f	f	f	42	1.5
Other group	b	b	b	b	b	f	2	0.1	7.2
	b	b	b	b	b&f	f	6	0.2
	b	b	b	b&f	b&f	f	3	0.1
	b	b	b&f	b&f	b&f	f	3	0.1
	b	b&f	b&f	b&f	b&f	f	3	0.1
	b	f	b	b	b&f	b&f	1	0.0
	b&f	b	b	b	b	f	1	0.0
	b&f	b&f	b	b&f	f	b&f	1	0.0
	b&f	b&f	b&f	b	b&f	f	1	0.0
	b&f	b&f	b&f	b&f	b&f	f	22	0.8
	b&f	b&f	b&f	f	b&f	b&f	1	0.0
	b&f	b&f	f	b	b	b	1	0.0
	b&f	f	b&f	b	b	b	2	0.1
	f	b	b	b	b	b	3	0.1
	f	b&f	b	b	b	b	2	0.1
	f	b&f	b&f	b&f	b&f	b&f	3	0.1
	b	b	b	b	f	f	2	0.1
	b	b	b	b&f	f	f	4	0.1
	b	b	b&f	b&f	f	f	2	0.1
	b	b&f	b&f	b&f	f	f	6	0.2
	b&f	b&f	b&f	b&f	f	f	43	1.6
	f	f	b	b	b	b	1	0.0
	b	b	b	f	f	f	14	0.5
	b	b	b&f	f	f	f	13	0.5
	b	b&f	b&f	f	f	f	9	0.3
	b&f	b	b&f	f	f	f	1	0.0
	b&f	b&f	b&f	f	f	f	43	1.6
	f	b	b	b	f	f	1	0.0
	f	b&f	b&f	b&f	f	f	1	0.0
	f	f	f	b&f	b&f	b&f	1	0.0
	f	f	f	b	b	b	1	0.0

Exclusive breastfeeding group: solely breastfeeding for 6 months.

Partial breastfeeding group: solely breastfeeding for ≤5 months and combination of breastfeeding and formula for the rest of months, including combination of breastfeeding and formula for 6 months.

Formula-fed group: solely formula feeding for ≥4 months. This group includes the following cases: solely formula feeding for 6 months or either solely breastfeeding or combining breastfeeding and formula for the first 1 or 2 months postpartum and solely formula for the later months.

Other group: participants who did not meet the conditions mentioned in the aforementioned three groups.

b, breastfeeding; b&f, combination of breastfeeding and formula-fed; f, formula-fed.

The reasons for including a formula-fed group were (1) the small number of children included in the “solely formula for 6 months” and “either solely breastfeeding or combination of breastfeeding and formula for the first 1 or 2 months postpartum and solely formula for the later months” groups (Table 2); and (2) in Japan, employers are prohibited by law from allowing women to work during the first 8 weeks postpartum.¹⁸ Therefore, we assumed that mothers who return to work after approximately the first 2 months postpartum may have to select an exclusive formula for the remaining 4 months.

Cognitive development in 2- and 4-year-old children

The KSPD, a standardized developmental assessment tool for Japanese children, covers the cognitive-adaptive (C-A) and language-social (L-S) areas of development.^11–16 The C-A and L-S areas correspond to nonverbal and verbal cognitive development, respectively. Scores were combined to form the developmental quotient (DQ), calculated (in days) by dividing the developmental age in days by the chronological age and multiplying by 100. Administrative procedures and evaluations were strictly standardized to ensure tester reliability in this survey. The testers received rigorous training before being certified to conduct the testing to ensure the administration’s reliability. The testers were certified by the JECS.

Statistical analysis and covariables

We compared feeding methods and children’s cognitive development using an analysis of variance (ANOVA). Bivariate and multiple regression analyses were used to assess the association between feeding methods and children’s cognitive development.

The multiple regression analyses were adjusted for maternal age at delivery, whether the pregnancy was unplanned, use of infertility treatment, marital status, highest level of education (maternal and paternal), smoking during pregnancy (maternal and paternal), maternal alcohol consumption during pregnancy, annual household income, whether the mother had any neuropsychiatric disorders, psychoactive drug use during pregnancy, psychological intimate partner violence during pregnancy, physical intimate partner violence during pregnancy, maternal depression symptoms (Edinburgh Postnatal Depression Scale ≥9) at 6 months postpartum,^19,20 maternal bonding failure (Mother–Infant Bonding Scale scores ≥5) at 1 year postpartum,^21,22 whether pregnancy complications occurred, whether obstetric labor complications occurred, mode of delivery, children’s birth weight, gestational week of delivery, family structure, number of siblings (including the participant), children’s age at beginning attendance at a daycare center, location of the Regional Center, and children’s sex for overall. These confounding factors were based on previous studies.⁶ No multicollinearity was observed in the analysis. For reference, parity and the number of children were multicollinear.

All analyses were performed using SAS statistical software (version 9.4; SAS Institute Inc.).

Results

Overview

Of the 104,059 records in the dataset, those of 2,727 children from singleton pregnancies without preterm birth (delivery of <37 weeks of pregnancy) and congenital anomalies who had undergone evaluation using the KSPD at ages 2 and 4 years were analyzed (Fig. 1). Table 1 shows the participants’ characteristics. In total, there were 1,329 boys and 1,398 girls. Overall, 1,240 (45.5%) participants were included in the exclusive breastfeeding group, 1,111 (40.7%) in the partial breastfeeding group, 179 (6.6%) in the formula-fed group, and 197 (7.2%) in the other group. Table 2 shows the details of the participants’ feeding method status during the first 6 months postpartum. Table 3 shows the results of the one-way ANOVA for feeding methods and children’s KSPD scores. Table 4 shows bivariate analysis results for feeding methods and children’s KSPD scores.

FIG. 1.

Flow chart depicting research participants’ selection. KSPD, Kyoto Scale of Psychological Development 2001.

Table 3.

ANOVA of Feeding Method for the First 6 Months Postpartum and KSPD at Age 2 and 4 Years

		Feeding method during 6 months postpartum	n	%	Mean ± SD	p
Boys	C-A DQ at age 2 years	Exclusive breastfeeding	599	45.1	95.2 ± 11.9	0.12
n = 1,329		Partial breastfeeding	548	41.2	93.7 ± 11.7
		Formula-fed	81	6.1	93.2 ± 10.7
		Other	101	7.6	93.9 ± 11.3
	L-S DQ at age 2 years	Exclusive breastfeeding	599	45.1	91.2 ± 13.3	0.046
		Partial breastfeeding	548	41.2	90.8 ± 15.7
		Formula-fed	81	6.1	86.4 ± 13.8
		Other	101	7.6	90.5 ± 14.4
	C-A DQ at age 4 years	Exclusive breastfeeding	599	45.1	96.2 ± 14.9	0.18
		Partial breastfeeding	548	41.2	95.4 ± 15.0
		Formula-fed	81	6.1	92.9 ± 11.7
		Other	101	7.6	94.1 ± 14.0
	L-S DQ at age 4 years	Exclusive breastfeeding	599	45.1	95.1 ± 16.3	0.60
		Partial breastfeeding	548	41.2	95.8 ± 16.1
		Formula-fed	81	6.1	93.3 ± 14.1
		Other	101	7.6	95.3 ± 15.1
Girls	C-A DQ at age 2 years	Exclusive breastfeeding	641	45.9	98.8 ± 12.7	0.40
n = 1,398		Partial breastfeeding	563	40.3	98.5 ± 13.0
		Formula-fed	98	7.0	96.6 ± 12.7
		Other	96	6.9	97.6 ± 11.2
	L-S DQ at age 2 years	Exclusive breastfeeding	641	45.9	96.5 ± 13.8	0.15
		Partial breastfeeding	563	40.3	96.9 ± 15.3
		Formula-fed	98	7.0	93.5 ± 15.4
		Other	96	6.9	95.1 ± 14.4
	C-A DQ at age 4 years	Exclusive breastfeeding	641	45.9	98.7 ± 13.5	0.07
		Partial breastfeeding	563	40.3	97.4 ± 13.7
		Formula-fed	98	7.0	95.5 ± 12.3
		Other	96	6.9	96.4 ± 12.9
	L-S DQ at age 4 years	Exclusive breastfeeding	641	45.9	98.5 ± 14.7	0.01
		Partial breastfeeding	563	40.3	98.3 ± 14.9
		Formula-fed	98	7.0	93.2 ± 14.9
		Other	96	6.9	97.8 ± 13.5
Overall	C-A DQ at age 2 years	Exclusive breastfeeding	1,240	45.5	97.0 ± 12.4	0.09
n = 2,727		Partial breastfeeding	1,111	40.7	96.1 ± 12.6
		Formula-fed	179	6.6	95.1 ± 11.9
		Other	197	7.2	95.7 ± 11.3
	L-S DQ at age 2 years	Exclusive breastfeeding	1,240	45.5	93.9 ± 13.8	0.01
		Partial breastfeeding	1,111	40.7	93.9 ± 15.8
		Formula-fed	179	6.6	90.3 ± 15.1
		Other	197	7.2	92.7 ± 14.5
	C-A DQ at age 4 years	Exclusive breastfeeding	1,240	45.5	97.5 ± 14.2	0.01
		Partial breastfeeding	1,111	40.7	96.4 ± 14.4
		Formula-fed	179	6.6	94.3 ± 12.1
		Other	197	7.2	95.3 ± 13.5
	L-S DQ at age 4 years	Exclusive breastfeeding	1,240	45.5	96.8 ± 15.6	0.02
		Partial breastfeeding	1,111	40.7	97.0 ± 15.5
		Formula-fed	179	6.6	93.3 ± 14.5
		Other	197	7.2	96.5 ± 14.4

ANOVA, analysis of variance; KSPD, Kyoto Scale of Psychological Development 2001; SD, standard deviation; DQ, developmental quotient; C-A, cognitive-adaptive; L-S, language-social.

Table 4.

Bivariate Analysis of Feeding Method for the First 6 Months Postpartum and KSPD at Ages 2 and 4 Years

		Feeding method during6 months postpartum	Pr > F	R ²	B	95%CI	β	p	VIF
Boys	C-A DQ at age 2 years	Exclusive breastfeeding	0.12	0.004	Ref
n = 1,329		Partial breastfeeding			−1.535	−2.889, −0.181	−0.065	0.03	1.1
		Formula-fed			−1.962	−4.674, 0.749	−0.040	0.16	1.1
		Other			−1.266	−3.730, 1.198	−0.029	0.31	1.1
	L-S DQ at age 2 years	Exclusive breastfeeding	0.046	0.006	Ref
		Partial breastfeeding			−0.424	−2.099, 1.251	−0.014	0.62	1.1
		Formula-fed			−4.823	−8.178, −1.468	−0.080	0.005	1.1
		Other			−0.775	−3.823, 2.273	−0.014	0.62	1.1
	C-A DQ at age 4 years	Exclusive breastfeeding	0.18	0.004	Ref
		Partial breastfeeding			−0.845	−2.548, 0.858	−0.028	0.33	1.1
		Formula-fed			−3.351	−6.762, 0.059	−0.055	0.054	1.1
		Other			−2.067	−5.166, 1.032	−0.037	0.19	1.1
	L-S DQ at age 4 years	Exclusive breastfeeding	0.60	0.001	Ref
		Partial breastfeeding			0.728	−1.128, 2.585	0.022	0.44	1.1
		Formula-fed			−1.714	−5.432, 2.003	−0.026	0.37	1.1
		Other			0.197	−3.181, 3.575	0.003	0.91	1.1
Girls	C-A DQ at age 2 years	Exclusive breastfeeding	0.40	0.002	Ref
n = 1,398		Partial breastfeeding			−0.268	−1.712, 1.176	−0.010	0.72	1.1
		Formula-fed			−2.160	−4.871, 0.551	−0.043	0.12	1.1
		Other			−1.220	−3.956, 1.515	−0.024	0.38	1.1
	L-S DQ at age 2 years	Exclusive breastfeeding	0.15	0.004	Ref
		Partial breastfeeding			0.460	−1.191, 2.110	0.015	0.58	1.1
		Formula-fed			−2.951	−6.049, 0.148	−0.052	0.06	1.1
		Other			−1.357	−4.483, 1.770	−0.024	0.39	1.1
	C-A DQ at age 4 years	Exclusive breastfeeding	0.07	0.005	Ref
		Partial breastfeeding			−1.295	−2.819, 0.229	−0.047	0.10	1.1
		Formula-fed			−3.165	−6.027, −0.304	−0.060	0.03	1.1
		Other			−2.228	−5.115, 0.660	−0.042	0.13	1.1
	L-S DQ at age 4 years	Exclusive breastfeeding	0.01	0.008	Ref
		Partial breastfeeding			−0.230	−1.894, 1.435	−0.008	0.79	1.1
		Formula-fed			−5.280	−8.405, −2.154	−0.092	0.001	1.1
		Other			−0.702	−3.856, 2.451	−0.012	0.66	1.1
Overall	C-A DQ at age 2 years	Exclusive breastfeeding	0.09	0.002	Ref
n = 2,727		Partial breastfeeding			−0.929	−1.933, 0.075	−0.037	0.07	1.1
		Formula-fed			−1.961	−3.905, −0.017	−0.039	0.048	1.1
		Other			−1.350	−3.214, 0.515	−0.028	0.16	1.1
	L-S DQ at age 2 years	Exclusive breastfeeding	0.01	0.004
		Partial breastfeeding			−0.030	−1.226, 1.167	−0.001	0.96	1.1
		Formula-fed			−3.638	−5.954, −1.322	−0.061	0.002	1.1
		Other			−1.214	−3.436, 1.008	−0.021	0.28	1.1
	C-A DQ at age 4 years	Exclusive breastfeeding	0.01	0.004
		Partial breastfeeding			−1.098	−2.240, 0.044	−0.038	0.06	1.1
		Formula-fed			−3.174	−5.385, −0.963	−0.056	0.005	1.1
		Other			−2.218	−4.339, −0.097	−0.041	0.04	1.1
	L-S DQ at age 4 years	Exclusive breastfeeding	0.02	0.004
		Partial breastfeeding			0.208	−1.040, 1.456	0.007	0.74	1.1
		Formula-fed			−3.562	−5.976, −1.147	−0.057	0.004	1.1
		Other			−0.343	−2.659, 1.974	−0.006	0.77	1.1

KSPD, Kyoto Scale of Psychological Development 2001; DQ, developmental quotient; C-A, cognitive-adaptive; L-S, language-social; SD, standard deviation; B, partial regression coefficient; CI, confidence interval; β, standardized partial regression coefficients; VIF, variance inflation factor.

Boys of age 2 years

Multiple regression analysis showed that boys of age 2 years in the formula-fed group had significantly lower L-S DQ scores (partial regression coefficient [B]: −4.624, 95% confidence interval [CI]: −8.005 to −1.243, β: −0.076, p = 0.01) than those in the exclusive breastfeeding group (Table 5). However, partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Table 5.

Multiple Regression Analysis of Feeding Method for the First 6 Months Postpartum and KSPD at Ages 2 and 4 Years

		Feeding method during six months postpartum	Pr > F	R ²	B	95%CI	β	p	VIF
Boys	C-A DQ at age 2 years	Exclusive breastfeeding	<0.0001	0.074	Ref
n = 1,329		Partial breastfeeding			−1.156	−2.529, 0.216	−0.049	0.10	1.2
		Formula-fed			−0.808	−3.563, 1.948	−0.017	0.57	1.1
		Other			−0.909	−3.430, 1.612	−0.021	0.48	1.2
	L-S DQ at age 2 years	Exclusive breastfeeding	<0.0001	0.090	Ref
		Partial breastfeeding			−0.867	−2.551, 0.816	−0.030	0.31	1.2
		Formula-fed			−4.624	−8.005, −1.243	−0.076	0.01	1.1
		Other			−1.005	−4.098, 2.087	−0.018	0.52	1.2
	C-A DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.106	Ref
		Partial breastfeeding			0.020	−1.682, 1.721	0.001	0.98	1.2
		Formula-fed			−0.864	−4.273, 2.545	−0.014	0.62	1.1
		Other			−0.007	−3.123, 3.110	0.000	1.00	1.2
	L-S DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.103	Ref
		Partial breastfeeding			0.507	−1.350, 2.363	0.016	0.59	1.2
		Formula-fed			−0.029	−3.748, 3.689	0.000	0.99	1.1
		Other			1.535	−1.864, 4.934	0.025	0.38	1.2
Girls	C-A DQ at age 2 years	Exclusive breastfeeding	0.01	0.051	Ref
n = 1,398		Partial breastfeeding			0.104	−1.388, 1.597	0.004	0.89	1.2
		Formula-fed			−1.564	−4.426, 1.297	−0.031	0.28	1.2
		Other			−1.607	−4.425, 1.212	−0.032	0.26	1.2
	L-S DQ at age 2 years	Exclusive breastfeeding	<0.0001	0.092	Ref
		Partial breastfeeding			−0.293	−1.963, 1.376	−0.010	0.73	1.2
		Formula-fed			−3.637	−6.838, −0.435	−0.064	0.03	1.2
		Other			−2.247	−5.400, 0.907	−0.039	0.16	1.2
	C-A DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.097	Ref
		Partial breastfeeding			−0.517	−2.057, 1.023	−0.019	0.51	1.2
		Formula-fed			−0.618	−3.571, 2.335	−0.012	0.68	1.2
		Other			−1.049	−3.953, 1.856	−0.020	0.48	1.2
	L-S DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.154	Ref
		Partial breastfeeding			−0.590	−2.220, 1.041	−0.020	0.48	1.2
		Formula-fed			−3.414	−6.540, −0.288	−0.059	0.03	1.2
		Other			−0.255	−3.330, 2.820	−0.004	0.87	1.2
Overall	C-A DQ at age 2 years	Exclusive breastfeeding	<0.0001	0.073	Ref
n = 2,727		Partial breastfeeding			−0.483	−1.489, 0.522	−0.019	0.35	1.2
		Formula-fed			−1.246	−3.216, 0.723	−0.025	0.21	1.2
		Other			−1.167	−3.028, 0.694	−0.024	0.22	1.1
	L-S DQ at age 2 years	Exclusive breastfeeding	<0.0001	0.107	Ref
		Partial breastfeeding			−0.460	−1.637, 0.717	−0.015	0.44	1.2
		Formula-fed			−4.037	−6.342, −1.732	−0.068	0.001	1.2
		Other			−1.520	−3.699, 0.658	−0.027	0.17	1.1
	C-A DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.089	Ref
		Partial breastfeeding			−0.369	−1.506, 0.768	−0.013	0.52	1.2
		Formula-fed			−0.703	−2.925, 1.520	−0.012	0.54	1.2
		Other			−0.565	−2.664, 1.535	−0.010	0.60	1.1
	L-S DQ at age 4 years	Exclusive breastfeeding	<0.0001	0.115	Ref
		Partial breastfeeding			−0.071	−1.295, 1.152	−0.002	0.91	1.2
		Formula-fed			−1.827	−4.217, 0.563	−0.029	0.13	1.2
		Other			0.743	−1.515, 3.002	0.012	0.52	1.1

Adjusted for age of mother at the delivery, unplanned pregnancy, infertility treatment, marital status, maternal highest level of education, paternal highest level of education, maternal smoking during pregnancy, paternal smoking during pregnancy, maternal alcohol consumption during pregnancy, annual household income, maternal neuropsychiatric disorders, psychoactive drug use during pregnancy, psychological intimate partner violence during pregnancy, physical intimate partner violence during pregnancy, depression symptoms (Edinburgh Postnatal Depression Scale scores ≥9) at postpartum 6 months, bonding failure (Mother, Infant Bonding Scale scores ≥5) at postpartum 1 year, pregnancy complications, obstetric labor complications, mode of delivery, birth weight of children, family structure, number of children included participant, attendance age of daycare center at age 2 years (for C-A, L-S DQ at age 2 years), attendance age of daycare center at age 4 years (for C-A, L-S DQ at age 4 years), location of the Regional Center, and sex of children for overall.

KSPD, Kyoto Scale of Psychological Development 2001; DQ, developmental quotient; C-A, cognitive-adaptive; L-S, language-social; B, partial regression coefficient; CI, confidence interval; β, standardized partial regression coefficients; VIF, variance inflation factor.

Boys of age 4 years

Multiple regression analysis showed that boys of age 4 years in the formula-fed group did not have significantly lower L-S DQ scores than those in the exclusive breastfeeding group (Table 5). The partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Girls of age 2 years

Multiple regression analysis showed that girls of age 2 years in the formula-fed group had significantly lower L-S DQ scores (B: −3.637, 95% CI: −6.838 to −0.435, β: −0.064, p = 0.03) than those in the exclusive breastfeeding group (Table 5). The partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Girls of age 4 years

Multiple regression analysis showed that girls of age 4 years in the formula-fed group had significantly lower L-S DQ scores (B: −3.414, 95% CI: −6.540 to −0.288, β: −0.059, p = 0.03) than those in the exclusive breastfeeding group (Table 5). The partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Overall participants of age 2 years

Multiple regression analysis showed that the formula-fed group (overall participants of age 2 years) had significantly lower L-S DQ scores (B: −4.037, 95% CI: −6.342 to −1.732, β: −0.068, p = 0.001) than the exclusive breastfeeding group (Table 5). The partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Overall participants of age 4 years

Multiple regression analysis showed that the formula-fed group (overall participants of age 4 years) did not have significantly lower L-S DQ scores than the exclusive breastfeeding group (Table 5). The partial feeding and other groups did not significantly differ from the exclusive breastfeeding group in L-S DQ scores (Table 5). All groups did not significantly differ from the exclusive breastfeeding group in C-A DQ scores.

Discussion

This study suggests that exclusive breastfeeding for the first 6 months postpartum may be more beneficial for verbal cognitive development in 2- and 4-year-old girls than solely formula feeding for ≥4 months. In contrast, exclusive breastfeeding for the first 6 months postpartum may benefit verbal cognitive development in 2-year-old boys than solely formula feeding for ≥4 months; however, no significant benefit was found in 4-year-old boys.

Notably, cognitive development in any area did not differ between the partial and exclusive breastfeeding groups, regardless of age. This indicates that breastfeeding combined with formula for the first 6 months postpartum may not have a disadvantage on cognitive development in boys and girls of age ≥ 2 years compared with exclusive breastfeeding during the first 6 months postpartum.

Regarding exclusive or any other breastfeeding method, previous studies from different countries have provided evidence for the association between breastfeeding and cognitive development.⁷ A cluster-randomized trial in the Republic of Belarus suggested, with strong evidence, that prolonged and exclusive breastfeeding improves children’s cognitive development at the age of 6.5 years.⁵ An Australian cohort study reported that verbal cognitive development was higher in 6-year-old children who were exclusively breastfed for >6 months than in those who were never breastfed.⁴ A Philippine cohort study reported that an increased duration of breastfeeding was of small significant benefit to children’s cognitive development at ages 8.5 and 11.5 years.²³ A cohort study in the United Kingdom reported that breastfeeding was associated with intelligence quotient (IQ) at the age of 4 years.²⁴ A cohort study in the United States also reported that breastfeeding duration was associated with receptive language and verbal and nonverbal intelligence at the age of 7 years.²⁵ A French cohort study reported that a longer breastfeeding duration was associated with better cognitive development and a dose–response relationship at ages 2 and 3 years.²⁶

One possible reason for the beneficial effects of breast milk is that the components of breast milk itself, particularly the long-chain polyunsaturated fatty acids, which are present in breast milk but usually absent in formula, may contribute to enhanced patterns of myelination in the developing brain.²⁷ However, this does not fully explain the effect of breastfeeding on brain development. Therefore, factors contributing to the beneficial effects of breastfeeding include aspects of mother–infant interaction, such as touch and warmth, and other substrates in breast milk, such as hormones, that are not present in formula.⁷

Furthermore, previous studies from different countries have reported a negative association between breastfeeding and cognitive development. A national longitudinal survey in the United States revealed that breastfeeding had little or no effect on intelligence between the ages of 5 and 14.²⁸ An Australian cohort study reported no association between breastfeeding duration and childhood IQ at the age of 4 years.²⁹ The Twins Early Development Study in the United Kingdom reported that breastfeeding was of little benefit to early life intelligence and cognitive growth from toddlerhood to adolescence (of age 2–16 years).³⁰ An Irish cohort study reported that breastfeeding was not significantly associated with cognitive development at ages 3 and 5 years.³¹ A Danish cohort study also reported that a breastfeeding duration of ≤1 month was associated with approximately three-point lower IQ than longer periods; however, there was no evidence of a dose–response relationship at the age of 5 years.³²

However, these previous studies did not examine sex-based differences. Our JECS in Japan found a beneficial association between breastfeeding and verbal cognitive development in both boys and girls of age 2 years but only in girls of age 4 years. It is presently unclear whether this difference is due to differences in sensitivity to breastfeeding or in child-rearing methods based on sex differences. Therefore, further research is required in this regard.

Limitations

This study had several limitations. First, the Sub-Cohort Study was based on a 5% extraction of 104,059 records in the dataset. In total, 2,727 (2.6%) participants were included in the current study, and there may have been an intrinsic bias in the subsample used. Second, the differences in child-rearing practices between boys and girls were not examined.

Strengths of the study

This was a large, prospective birth cohort study in which certified testers objectively assessed the cognitive development of 2,727 children of age 2 and 4 years. Sex-based differences were also observed.

Conclusion

Exclusive breastfeeding for the first 6 months postpartum may be more beneficial for verbal cognitive development in 2- and 4-year-old girls than solely formula feeding for ≥4 months. In contrast, exclusive breastfeeding for the first 6 months postpartum may be more beneficial for verbal cognitive development in 2-year-old boys than solely formula feeding for ≥4 months; however, no significant benefit was observed in boys of age 4 years.

Furthermore, breastfeeding combined with formula for the first 6 months postpartum may not have a disadvantage on cognitive development in boys and girls of age ≥ 2 years, when compared with that observed with exclusive breastfeeding during the first 6 months postpartum.

Footnotes

Acknowledgments

The authors are grateful to all the participants of the study. Members of the JECS group as of 2022 are as follows: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Tomotaka Sobue (Osaka University, Suita, Japan), Masayuki Shima (Hyogo Medical University, Nishinomiya, Japan), Hiroshige Nakamura (Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Koichi Kusuhara (University of Occupational and Environmental Health, Kitakyushu, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan).

Authors’ Contributions

T.N. and H.N.: designed the study. T.N., H.N., T.S., H.K., Y.O., A.S., Y.N., S.Y., K.F., M.H., and K.H.: carried out the study. T.N. analyzed the data. T.N., H.N., T.S., T.F., T.M., H.K., Y.O., A.S., Y.N., S.Y., K.F., M.H., and K.H.: interpreted the findings. T.N. and H.N.: wrote the paper. All authors read and approved the final version of the article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the opinions of the authors and do not represent the official views of the above government.

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