nutrients

Article
Breastfeeding, Gestational Diabetes Mellitus, Size at Birth and
Overweight/Obesity in Early Childhood
Ye Huang 1,2 , Libi Zhang 1,2 , Diliyaer Ainiwan 1,2 , Xialidan Alifu 1,2 , Haoyue Cheng 1,2 , Yiwen Qiu 1,2 ,
Haibo Zhou 1,2 , Hui Liu 3 and Yunxian Yu 1,2, *

1 Department of Public Health and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang
University School of Medicine, Hangzhou 310009, China; 22218854@zju.edu.cn (Y.H.);
22218857@zju.edu.cn (L.Z.); 22218236@zju.edu.cn (D.A.); 3130100017@zju.edu.cn (X.A.);
3150101365@zju.edu.cn (H.C.); yiwenqiu@zju.edu.cn (Y.Q.); 11918158@zju.edu.cn (H.Z.)
2 Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang
University, Hangzhou 310058, China
3 Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China;
lhui2010@zju.edu.cn
* Correspondence: yunxianyu@zju.edu.cn

Abstract: Background: Breastfeeding appears to reduce the risk of childhood overweight/obesity.

However, it remains unclear whether this protective effect persists among high-risk populations.
This study aims to investigate the association of breastfeeding with the risk of overweight/obesity
in early childhood and whether this association is altered by gestational diabetes mellitus (GDM)
or size at birth. Methods: Feeding practices during the first 12 months of age and weight and
length at 12–36 months of age were collected. Full breastfeeding includes exclusive and predominant
breastfeeding. Children with body mass index (BMI) values greater than 1 standard deviation from
the mean of sex- and age-specific BMI were classified as overweight/obese. Multiple generalized
estimating equations models were applied to analyze the associations of full breastfeeding duration
with overweight/obesity risk. Results: Among all participants (n = 9329), infants with a longer
full-breastfeeding duration had a reduced risk of overweight/obesity in early childhood compared
with those breastfed for less than one month. Infants exposed to GDM and those born large for
Citation: Huang, Y.; Zhang, L.;
gestational age (LGA) had a higher risk of overweight/obesity in early childhood. Among infants
Ainiwan, D.; Alifu, X.; Cheng, H.; Qiu,
of mothers with GDM (n = 1748), infants with full breastfeeding for greater than 6 months (aOR:
Y.; Zhou, H.; Liu, H.; Yu, Y.
0.58; 95% CI: 0.44, 0.78) showed a decreased risk of overweight/obesity in early childhood compared
Breastfeeding, Gestational Diabetes
with those breastfed for less than one month. Among LGA infants (n = 1279), infants with full
Mellitus, Size at Birth and
Overweight/Obesity in Early breastfeeding for 3–5 months (aOR: 0.66; 95% CI: 0.57, 0.76) and greater than 6 months (aOR: 0.70;
Childhood. Nutrients 2024, 16, 1351. 95% CI: 0.56, 0.88) showed a decreased risk of overweight/obesity in early childhood. Similar results
https://doi.org/10.3390/nu16091351 were observed among LGA infants of mothers with GDM. Conclusions: Initiating and prolonging
breastfeeding would reduce the risk of overweight/obesity in early childhood, and LGA infants and
Academic Editor: Andrea Vania
infants born to mothers with GDM would experience greater benefits.
Received: 5 April 2024
Revised: 24 April 2024 Keywords: breastfeeding; gestational diabetes mellitus; size at birth; overweight/obesity; early
Accepted: 28 April 2024 childhood
Published: 30 April 2024

1. Introduction
Copyright: © 2024 by the authors.
The increasing prevalence of childhood overweight and obesity has become a pressing
Licensee MDPI, Basel, Switzerland.
This article is an open access article
global public health issue, particularly in China [1,2]. The development of obesity is
distributed under the terms and
influenced by complex factors, including lifestyle habits, dietary patterns, and genetic
conditions of the Creative Commons
predispositions [2,3]. Among these factors, the infancy stage has been identified as a critical
Attribution (CC BY) license (https:// and sensitive time window for future health [4]. Consequently, understanding the impact
creativecommons.org/licenses/by/ of infant nutrition and implementing targeted interventions has gradually become a focal
4.0/). point in research. Some previous studies have suggested that breastfeeding may have an

Nutrients 2024, 16, 1351. https://doi.org/10.3390/nu16091351 https://www.mdpi.com/journal/nutrients

Nutrients 2024, 16, 1351 2 of 11

impact on later health. For example, infants breastfed for longer duration have been shown
to exhibit different growth trajectories [5] and neurological developments [6] compared
with those breastfed for shorter periods or those fed with infant formula milk. Additionally,
several studies have indicated that breastfeeding may have a protective effect against the
development of obesity [7–9].
However, some research indicates that breast milk from mothers with hyperglycemia
may alter metabolic hormone concentrations [10], which could potentially affect energy
metabolism and influence the correlation between breastfeeding and offspring growth.
Currently, several observational studies evaluating the association of breastfeeding with
childhood overweight/obesity among women with gestational diabetes mellitus (GDM)
have yielded mixed results [11–14]. For example, Gunderson et al. found that high-intensity
breastfeeding during the first year was associated with reduced weight gain among off-
spring of mothers with GDM [12]. Conversely, another study reported that greater breast-
milk intake was associated with greater weight and body mass index (BMI) gains among
infants born to mothers with GDM [14]. Thus, in situations where breastfeeding is highly
recommended, it is imperative to further explore the impact of breastfeeding on later
overweight/obesity among offspring of mothers with GDM. In addition, size at birth,
particularly being large for gestational age (LGA), was demonstrated to be closely linked
to the onset of childhood obesity [15,16]. However, limited research exists that evaluates
whether size at birth could alter the effect of breastfeeding on overweight/obesity.
As an in-depth supplement to existing literature, this study aims to investigate the
correlation between breastfeeding and being overweight/obese in early childhood and
to explore whether this association would be altered by GDM status or size at birth. By
doing this, this research endeavors to provide a more comprehensive understanding of the
impact of breastfeeding on offspring overweight/obesity.

2. Method
2.1. Study Design and Data Source
This is a population-based retrospective cohort study. Data were extracted from
the comprehensive electronic medical record system (EMRS) of Zhoushan Maternal and
Child Care Hospital, Zhejiang Province, China from 2012 to 2021. The EMRS was a
municipal system established in 2001 and included information on the health care of all
pregnant women and newborns in Zhoushan city after 2011 [17,18]. Briefly, according to
the guidelines of Zhoushan Maternal and Child Care Hospital, the information on pregnant
women was recorded in the EMRS at each regular antenatal visit, during delivery, and
postpartum. Meanwhile, the information on offspring was collected at birth and at each
required visit to child healthcare units (i.e., at 1, 3, 6, 9, 12, 18, 24, 30, and 36 months).
The socio-demographic and health-related characteristics of pregnant women were
obtained from the prenatal health dataset from the EMRS. The information about the birth
condition, postnatal feeding, and growth of the children were obtained from the birth
registration information dataset and the conventional child health examination dataset
from the EMRS. The study protocol was approved by the institutional review board of
Zhejiang University School of Medicine (No. 2011-1-002).

2.2. Study Population

Participants who met the following criteria were included in the study: (1) maternal
age ≥ 18 years old; (2) live singleton pregnancy; (3) gestational weeks of delivery between
37 and 42 weeks; (4) offspring had two or more health examination records (i.e., height
and weight) between 12 and 36 months of age; (5) the feeding practices of offspring were
recorded at each required visit before 12 months of age.
The exclusion criteria included: (1) maternal BMI in the first trimester <15 kg/m2 or
>40 kg/m2 ; (2) offspring with congenital disease, chromosomal defects, or intrauterine
infections; (3) abnormal data that could not be linked to the maternal prenatal health
dataset, birth registration information, and conventional child health examination dataset.
Nutrients 2024, 16, 1351 3 of 11

2.3. Definition of Exposure Variables

In the process of data collection for this study, the feeding practices were categorized
as full breastfeeding, partial breastfeeding, or formula feeding during the required health
examination at 1, 3, 6, 9, and 12 months of age. According to the definition from the World
Health Organization (WHO), breastfeeding practices are classified as exclusive, predomi-
nant, or partial breastfeeding [19,20]. Exclusive breastfeeding is defined as the provision
of breast milk with no other liquids or solids, except for drops or liquid preparations
containing vitamins, oral rehydration solutions, mineral supplements, or medications.
Predominant breastfeeding is defined as the provision of breast milk, with the potential
consumption of water or water-based drinks, fruit juice, oral rehydration salts, and drop
or syrup forms of vitamins, minerals, and medicines. Partial breastfeeding is defined
as infants fed with, but not limited to, breast milk and formula milk. In this study, the
definition of full breastfeeding consists of exclusive and predominant breastfeeding [7].
Then, the duration of full breastfeeding was further categorized as <1 month, 1–2 months,
3–5 months and ≥6 months.
Pregnant women were required to receive a general screening for GDM with a 75 g
oral glucose tolerance test (OGTT) at 24–28 weeks [21]. GDM was diagnosed by either a
fasting glucose value ≥ 5.1 mmol/L, a 1 h post glucose value ≥ 10.0 mmol/L, or a 2 h post
glucose value ≥ 8.5 mmol/L, according to the International Association for Diabetes in
Pregnancy Study Groups (IADPSG) criteria [22].
Small for gestational age (SGA) infants, appropriate for gestational age (AGA) infants,
and LGA infants were defined as those infants having an infant birth weight below the
10th percentile, between the 10th and 90th percentile, and above the 90th percentile of
gestational age and gender-specific birth weights, respectively [23].

2.4. Definition of Overweight/Obesity

The measurements of weight (kg) and length (cm) were taken by specially trained
research nurses at each child health examination. The BMI (kg/m2 ) was calculated as
the weight divided by the length squared. According to the reference provided by the
National Health Commission of the People’s Republic of China [24], children with BMI
values greater than 1 standard deviation (SD) from the mean of sex- and age-specific BMI
were classified as overweight/obese.

2.5. Covariates
The following variables were investigated as potential confounders: maternal age,
maternal educational levels, early-pregnancy BMI, weight gain during pregnancy, parity,
gravidity, hypertensive disorders of pregnancy, neonatal gender, gestational weeks at
delivery, mode of delivery, and anthropometric measurements at 9 months of age.

2.6. Statistical Analysis

Continuous variables and categorical variables were expressed as the mean ± SD
and frequencies (proportion), respectively. ANOVA tests and Pearson chi-square tests
were applied to compare continuous variables and the distribution of categorical variables
among multiple groups, respectively. Generalized estimating equation (GEE) models with
an auto-regressive one-correlation structure were applied to analyze the associations of
the duration of full breastfeeding with the risk of overweight/obesity in offspring aged
between 12 and 36 months. The GEE model accounts for the correlation between repeated
measurements of overweight over time within subjects and deals with missing values.
The odds ratio (OR) and their 95% confidence intervals (CIs) for the association of full
breastfeeding and overweight/obesity were reported as in [25]. Then, the above models
were further adjusted for the covariates mentioned, and the adjusted ORs (aOR) with their
95% CIs were presented.
All analyses were performed using the statistical software R version 4.2.2. All statistical
tests were two-sided, and a p value of less than 0.05 was considered statistically significant.
Nutrients 2024, 16, 1351 4 of 11

3. Results
3.1. Baseline Characteristics
Baseline characteristics of participants stratified by full breastfeeding duration are
presented in Table 1. Among the total participants (n = 9329), 4368 (46.8%) were fully
breastfed for <1 month, 783 (8.4%) for 1–2 months, 3318 (35.6%) for 3–5 months, and only
860 (9.2%) for ≥6 months. The mothers of infants who were full breastfeeding for <1 month
were older and had a higher early-pregnancy BMI, along with a higher proportion of
cesarean deliveries.

Table 1. Baseline characteristics of participants, stratified by the duration of full breastfeeding.

Characteristics <1 Month 1–2 Months 3–5 Months ≥6 Months p

N (%) 4368 (46.8) 783 (8.4) 3318 (35.6) 860 (9.2)
Maternal age (years) 29.30 (4.09) 28.74 (4.06) 28.47 (3.72) 28.81 (3.70) <0.001
Early-pregnancy BMI (kg/m2 ) 21.38 (3.09) 21.14 (3.02) 21.19 (2.76) 21.30 (2.87) 0.023
BMI category (n, %) 0.001
Underweight and normal 3660 (83.8) 674 (86.1) 2886 (87.0) 726 (84.4)
Overweight and obese 708 (16.2) 109 (13.9) 432 (13.0) 134 (15.6)
Gravidity (n, %) 0.007
1 1985 (45.4) 357 (45.6) 1587 (47.8) 399 (46.4)
2 1149 (26.3) 193 (24.6) 881 (26.6) 218 (25.3)
3 682 (15.6) 126 (16.1) 511 (15.4) 159 (18.5)
≥4 552 (12.6) 107 (13.7) 339 (10.2) 84 (9.8)
Parity (n, %) <0.001
Primipara 2799 (64.1) 506 (64.6) 2217 (66.8) 543 (63.1)
Multipara 1197 (27.4) 230 (29.4) 903 (27.2) 264 (30.7)
Not known 372 (8.5) 47 (6.0) 198 (6.0) 53 (6.2)
Maternal educational levels (n, %) <0.001
Primary school or less 47 (1.1) 9 (1.1) 24 (0.7) 12 (1.4)
Junior high school 582 (13.3) 117 (14.9) 354 (10.7) 112 (13.0)
Senior high school 706 (16.2) 127 (16.2) 434 (13.1) 98 (11.4)
College or higher 2275 (52.1) 403 (51.5) 1983 (59.8) 503 (58.5)
Not known 758 (17.4) 127 (16.2) 523 (15.8) 135 (15.7)
Weight gain during pregnancy (kg) 12.95 (4.01) 12.92 (3.65) 12.99 (3.71) 12.59 (3.85) 0.057
Gestational diabetes mellitus (n, %) 0.006
No 3487 (79.8) 635 (81.1) 2752 (82.9) 707 (82.2)
Yes 881 (20.2) 148 (18.9) 566 (17.1) 153 (17.8)
Hypertensive disorders of pregnancy
0.058
(n, %)
No 4166 (95.4) 746 (95.3) 3199 (96.4) 831 (96.6)
Hypertensive disorder 141 (3.2) 25 (3.2) 87 (2.6) 22 (2.6)
Chronic hypertension 57 (1.3) 9 (1.1) 28 (0.8) 4 (0.5)
Eclampsia 4 (0.1) 3 (0.4) 4 (0.1) 3 (0.3)
Mode of delivery (n, %) <0.001
Vaginal delivery 2399 (54.9) 445 (56.8) 2178 (65.6) 556 (64.7)
Cesarean section 1969 (45.1) 338 (43.2) 1140 (34.4) 304 (35.3)
Neonatal gender (n, %) <0.001
Male 2413 (55.2) 407 (52.0) 1653 (49.8) 408 (47.4)
Female 1955 (44.8) 376 (48.0) 1665 (50.2) 452 (52.6)
Gestational age at delivery (years) 39.21 (1.14) 39.20 (1.16) 39.35 (1.10) 39.28 (1.12) <0.001
Neonatal birth weight (g) 3358.09 (401.91) 3329.66 (422.85) 3365.27 (392.47) 3343.01 (404.22) 0.105
Size at birth (n, %) 0.174
SGA infant 332 (7.6) 69 (8.8) 230 (6.9) 70 (8.1)
AGA infant 3405 (78.0) 606 (77.4) 2653 (80.0) 685 (79.7)
LGA infant 631 (14.4) 108 (13.8) 435 (13.1) 105 (12.2)
Abbreviation: AGA: appropriate for gestational age; BMI: body mass index; LGA: large for gestational age; SGA:
small for gestational age.

In comparison to infants of mothers without GDM (n = 7581), those of mothers with

GDM (n = 1748) had a higher proportion of full breastfeeding for <1 month (46.0% vs.
Nutrients 2024, 16, 1351 5 of 11

50.4%) and a lower proportion of full breastfeeding for ≥6 months (9.3% vs. 8.8%) (Table 1).
Similarly, compared with AGA infants (n = 7349), LGA infants (n = 1279) tended to have a
shorter full-breastfeeding duration, although the difference was not statistically significant
(Table 1).

3.2. Associations of the Duration of Full Breastfeeding with the Risk of Overweight/Obesity
between the Ages of 12–36 Months
Associations between full breastfeeding duration and the risk of overweight/obesity
for infants aged 12–36 months among all participants are presented in Table S1. In fully
adjusted models, infants with full breastfeeding for 3–5 months (aOR: 0.75; 95% CI: 0.71,
0.80) and ≥6 months (aOR: 0.85; 95% CI: 0.77, 0.93) were positively associated with a
reduced risk of overweight/obesity in early childhood compared with those with <1 month
of full breastfeeding.
In this study, infants exposed to GDM showed a higher risk of overweight/obesity
between the ages of 12–36 months compared with infants not exposed to GDM (aOR = 1.09;
95%CI: 1.01, 1.16). The associations of breastfeeding with the risk of overweight/obesity
in early childhood stratified by GDM status are displayed in Table 2. Among infants
whose mother did not have GDM, infants with full breastfeeding for 3–5 months (aOR:
0.87; 95% CI: 0.80, 0.94) and ≥6 months (aOR: 0.84; 95% CI: 0.74, 0.96) had a lower risk of
overweight/obesity compared with those with <1 month of full breastfeeding. Among
infants whose mother had GDM, infants with full breastfeeding for ≥6 months (aOR:
0.58; 95% CI: 0.44, 0.78) had a lower risk of overweight/obesity compared with those
with <1 month of full breastfeeding. We further investigated the combined effects of
breastfeeding and GDM status on early childhood overweight/obesity by a crossover
analysis (Table S2). In comparison with infants with full breastfeeding for <1 month and
whose mothers did not have GDM, those with full breastfeeding for ≥6 months and whose
mothers had GDM had a decreased risk of overweight/obesity in early childhood (aOR:
0.63; 95% CI: 0.48, 0.83).

Table 2. Associations between the duration of full breastfeeding and overweight/obesity in early
childhood, stratified by GDM status.

Duration N (%) OR (95% CI) aOR (95% CI)

Women without GDM
<1 month 2914 (19.0) Ref. Ref.
1–2 months 518 (18.5) 0.96 (0.87, 1.07) 1.04 (0.92, 1.18)
3–5 months 1724 (14.2) 0.70 (0.66, 0.75) 0.87 (0.80, 0.94)
≥6 months 495 (15.9) 0.80 (0.72, 0.89) 0.84 (0.74, 0.96)
Women with GDM
<1 month 788 (20.6) Ref. Ref.
1–2 months 125 (19.5) 0.94 (0.76, 1.16) 1.06 (0.82, 1.36)
3–5 months 335 (13.3) 0.59 (0.51, 0.68) 0.89 (0.75, 1.06)
≥6 months 105 (15.7) 0.72 (0.58, 0.90) 0.58 (0.44, 0.78)
P for interaction 0.034
Abbreviation: aOR: adjusted odds ratio; CI: confidence interval; GDM: gestational diabetes mellitus; OR: odds
ratio. Data adjusted for maternal age, maternal educational levels, parity, gravidity, hypertensive disorders of
pregnancy, neonatal gender, gestational age at delivery, mode of delivery, early-pregnancy body mass index,
weight gain during pregnancy, and related anthropometric measurements at 9 months.

In this study, LGA infants had a higher risk of overweight/obesity between

12–36 months (aOR = 1.45; 95%CI: 1.35, 1.56) compared with AGA infants, while SGA
infants had a lower risk (aOR = 0.51; 95%CI: 0.44, 0.59). The associations of breastfeeding
with the risk of overweight/obesity in early childhood stratified by size at birth are pre-
sented in Table 3. AGA infants who received full breastfeeding for 3–5 months (aOR: 0.73;
95% CI: 0.68, 0.78) and ≥6 months (aOR: 0.84; 95% CI: 0.75, 0.93) showed a decreased risk
of developing overweight/obesity compared with those who received <1 month of full
breastfeeding. Similarly, LGA infants who received full breastfeeding for 3–5 months (aOR:
Nutrients 2024, 16, 1351 6 of 11

0.66; 95% CI: 0.57, 0.76) and ≥6 months (aOR: 0.70; 95% CI: 0.56, 0.88) showed a decreased
risk of developing overweight/obesity compared with those with <1 month of full breast-
feeding. We further investigated the combined effects of breastfeeding and size at birth on
early childhood overweight/obesity by the crossover analysis (Table S3). In comparison
with AGA infants with <1 month of full breastfeeding, LGA infants who received 3–5
months and ≥6 months of full breastfeeding were no longer at risk of overweight/obesity
in early childhood.

Table 3. Associations between the duration of full breastfeeding and overweight/obesity in early
childhood, stratified by size at birth.

Duration N (%) OR (95% CI) aOR (95% CI)

SGA
<1 month 103 (7.1) Ref. Ref.
1–2 months 22 (7.5) 1.07 (0.66, 1.73) 1.41 (0.78, 2.53)
3–5 months 65 (6.4) 0.90 (0.65, 1.24) 1.03 (0.70, 1.51)
≥6 months 25 (7.9) 1.12 (0.71, 1.76) 0.89 (0.46, 1.70)
AGA
<1 month 2732 (18.3) Ref. Ref.
1–2 months 491 (18.3) 1.00 (0.89, 1.11) 1.02 (0.91, 1.13)
3–5 months 1539 (13.1) 0.67 (0.63, 0.72) 0.73 (0.68, 0.78)
≥6 months 452 (15.1) 0.79 (0.71, 0.88) 0.84 (0.75, 0.93)
LGA
<1 month 867 (31.3) Ref. Ref.
1–2 months 130 (28.0) 0.86 (0.69, 1.06) 0.86 (0.69, 1.08)
3–5 months 455 (23.5) 0.67 (0.59, 0.77) 0.66 (0.57, 0.76)
≥6 months 123 (25.6) 0.75 (0.60, 0.94) 0.70 (0.56, 0.88)
P for interaction <0.001
Abbreviation: aOR: adjusted odds ratio; AGA: appropriate for gestational age; CI: confidence interval; LGA: large
for gestational age; OR: odds ratio; SGA: small for gestational age. Data adjusted for maternal age, maternal
educational levels, parity, gravidity, gestational diabetes mellitus status, hypertensive disorders of pregnancy,
neonatal gender, gestational age at delivery, mode of delivery, early-pregnancy body mass index, weight gain
during pregnancy, and related anthropometric measurements at 9 months.

Considering the combination effect of GDM and LGA (referring to LGA infants born
to mothers with GDM), infants with full breastfeeding for 3–5 months (aOR: 0.62; 95% CI:
0.45, 0.85) and ≥6 months (aOR: 0.51; 95% CI: 0.31, 0.85) had a remarkably reduced risk of
overweight/obesity compared with those with <1 month of full breastfeeding (Table S4).

4. Discussion
In this study, we found that increased breastmilk intake duration was associated with
a reduced risk of overweight/obesity in early childhood. Meanwhile, our results indicated
that the protective effect of breastfeeding against overweight/obesity in early childhood re-
mained evident among LGA infants and infants born to mothers with GDM, and these high-
risk infants experienced even greater benefits from a longer full breastfeeding duration.
Currently, with the advancements in formula milk products and intensified marketing
efforts, breastfeeding faces unprecedented challenges in China [26–29]. Thus, emphasizing
and evaluating the importance of breastfeeding is a pressing need. Consistent with previous
studies [14,30–32], our finding confirmed the benefits of a longer exclusive/predominant
breastfeeding duration in decreasing the risk of overweight/obesity in early childhood.
These results support the recommendation from WHO’s global strategy that advocates
exclusive breastfeeding for 6 months [20]. However, it is important to note that there is no
consensus in the literature regarding the protective effects of breastfeeding against later
obesity. Although some researchers attribute this inconsistency to residual confounding
from variations in maternal sociodemographic characteristics [33], a recent meta-analysis
including 159 studies suggested that breastfeeding reduced the odds of overweight/obesity,
even after socioeconomic adjustments [34]. Thus, other external factors may contribute to
Nutrients 2024, 16, 1351 7 of 11

this inconsistency. In addition, the results reported that male offspring tended to receive
breastfeeding for a shorter duration compared with female offspring (deduced from the
boy/girl ratio in each group). However, this phenomenon is not consistent in previous
studies. For example, a study involving 57,201 children from seven provinces in China
showed that boys appeared to receive a longer duration of breastfeeding [35], while another
study suggested that girls might receive more breastfeeding [36]. Although we cannot
determine the exact reasons for the longer duration of breastfeeding in the female offspring
in this study, it may be because mothers perceive their sons as needing more nutrients,
potentially leading to the earlier introduction of formula milk or other foods, as speculated
by a nationwide study conducted in the United States [37].
Currently, the health consequences of breastfeeding by mothers with GDM remain con-
troversial. One study found that longer breastfeeding was linked to increased weight/BMI
gain from birth to 6 months in infants of mothers with GDM [14], while another study
showed no impact on the early-life growth trajectory [13]. Similar to other studies [12,38],
our findings suggest that breastfeeding for 6 months or longer significantly reduces the
overweight/obesity risk in early childhood among infants of mothers with GDM, and the
reduction in odds appears to be greater compared with infants of mothers without GDM.
The inconsistent results may result from different degrees of glucose control and postpar-
tum glycemia in GDM women across the various studies. Although data on postpartum
glycemia levels are lacking in this study, our findings suggest that a longer breastfeed-
ing duration is more likely to yield benefits than adverse effects in reducing the risk of
overweight/obesity among infants born to mothers with GDM. Additionally, our study sup-
ports previous findings indicating that GDM influences the breastfeeding duration [39,40].
In our study, the proportion of GDM women who fully breastfed their infants for more than
3 months was significantly lower than that of women without GDM (41.7% vs. 45.6%). This
disparity may be attributed to insulin resistance or inflammation in GDM women, which
may diminish prolactin responsiveness and lead to delayed lactogenesis and breastfeeding
initiation and maintenance [41,42].
LGA infants are at the greatest risk for future obesity, and research suggests that their
postnatal growth in early childhood may be linked to long-term adverse outcomes [43,44]. Thus,
promoting optimal postnatal growth is crucial for LGA infants. However, investigations
focusing on the effects of breastfeeding, as a highly recommended approach to nutrition
during the postnatal period, on early offspring overweight/obesity is limited. Our findings
revealed that a longer duration of full breastfeeding was associated with a reduced risk of
overweight/obesity in early childhood among AGA and LGA infants. This result confirmed
that breastfeeding might be an appropriate way to achieve optimal postanal growth for
LGA infants.
In fact, the potential mechanisms by which breastfeeding reduces the risk of child-
hood overweight/obesity are not fully elucidated. Extensive previous studies have sug-
gested that certain bioactive components in breast milk, such as leptin, adiponectin, and
insulin-like growth factor-1, may play important roles in reducing the risk of offspring
overweight/obesity [45]. Therefore, when explaining the association between breastfeeding
and early offspring weight gain among women with GDM, previous research also primarily
focused on the impact of changes in the breast milk composition in mothers with GDM,
such as the lower concentration of adiponectin [46,47]. However, epidemiological evidence
on the association between GDM status and milk composition remains inconsistent. Our
initial hypothesis was that perhaps the protective effect of breastfeeding against over-
weight/obesity may not remain in GDM pregnancies with suboptimal glycemic control.
Due to the lack of data on late-pregnancy glycemic control in our study, the presence of
LGA infants is considered indicative of more severe dysglycemia, as suggested by previous
research [48]. However, we found that breastfeeding in infants born to mothers with GDM
could still reduce the risk of overweight/obesity, even among those born LGA. This indi-
rectly suggests that breastfeeding still has a protective effect against overweight/obesity in
early childhood among poorly controlled GDM pregnancies. A recent prospective study
Nutrients 2024, 16, 1351 8 of 11

innovatively found that the level of glucose in the breast milk of GDM mothers decreases
compared with women without GDM, raising the speculation that milk glucose regulation
may, at least partially, be independent of maternal blood glucose [49]. Furthermore, another
study indicated that changes in breast milk composition mainly occur due to poor glycemic
control during breastfeeding [50]. This implies that changes in breast milk composition in
women with GDM may be temporary, with levels gradually returning to normal within
a few weeks after delivery [51]. These findings may help to explain why increasing the
duration of breastfeeding can still protect offspring born to mothers with GDM from the
adverse effects of overweight/obesity.
In this study, we provide data from a large retrospective cohort with standardized
procedures, and the findings underscore the importance of breastfeeding for early infant
development. This is particularly crucial at a time when there is a perception that breast-
feeding may not be necessary in modern urban settings. Meanwhile, considering that
feeding practices are potentially modifiable, our findings could carry significant public
health implications at a population level. In addition, we considered the effects of GDM
and size at birth to further address the inconsistencies and missing data in the literature.
However, some limitations still need to be noted. First, the report of feeding relied on recall
at each required visit, and potential recall bias could have been introduced. Nevertheless,
the recall of breastfeeding practices over a short period has been shown to be reliable [52].
Second, some potential confounders or variables, such as activity levels, time or sorts of
solid food introduction, or frequency of breastfeeding were not available in this study.
Meanwhile, we did not account for any treatments that women with GDM may have
received, nor did we differentiate the degree of postpartum glucose control.

5. Conclusions
In conclusion, this study suggests that initiating and prolonging breastfeeding would
reduce the risk of overweight/obesity in early childhood. Meanwhile, we observed that
LGA infants and infants of mothers with GDM would experience greater benefits from
a longer breastfeeding duration in terms of reducing the risk of overweight risk/obesity.
These findings highlight the importance of promoting breastfeeding as an intervention
against the epidemic of childhood overweight/obesity for high-risk populations. Further
research should be conducted to investigate the underlying biological mechanisms.

Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/nu16091351/s1, Table S1: Associations of the duration of full
breastfeeding and the risk of overweight/obesity in early childhood among all participants. Table S2:
Associations of GDM status and duration of full breastfeeding with the risk of overweight/obesity
in early childhood. Table S3: Associations of size at birth and the duration of full breastfeeding
with the risk of overweight/obesity in early childhood. Table S4: Associations of the duration of
full breastfeeding with the risk of overweight/obesity in early childhood, stratified by GDM status
during pregnancy and size at birth.
Author Contributions: Conceptualization, Y.H., Y.Y. and L.Z.; Methodology and Analysis, D.A. and
X.A.; Investigation and Data Curation, L.Z., H.C. and Y.Q.; Investigation, H.Z. and H.L.; Writing—
Original Draft Preparation, Y.H.; Writing—Review and Editing, Y.Y. All authors have read and agreed
to the published version of the manuscript.
Funding: This study was supported by the National Key Research and Development Programme of
China (2021YFC2701901, 2022YFC2703505); the 4+X Clinical Research Project of Women’s Hospital,
School of Medicine, Zhejiang University (ZDFY2021-4X104); the major research and development
projects of the Zhejiang Science and Technology Department (2018C03010); the Key Laboratory of
Intelligent Preventive Medicine of Zhejiang Province (2020E10004); and the Leading Innovative and
Entrepreneur Team Introduction Program of Zhejiang (2019R01007).
Institutional Review Board Statement: The study was conducted according to the guidelines of the
Declaration of Helsinki. This study protocol was approved by the institutional review board of the
Zhejiang University School of Medicine on 9 January 2011 (No. 2011-1-002).
Nutrients 2024, 16, 1351 9 of 11

Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study.
Data Availability Statement: All datasets generated during and analyzed during the current study
are not publicly available but are available from the corresponding author upon reasonable request.
Acknowledgments: We express our appreciation to all participants and their families, and we would
like to express our thanks to the medical staff for their dedication and hard work.
Conflicts of Interest: The authors declare no conflicts of interest.

References
1. GBD Obesity Collaborators; Afshin, A.; Forouzanfar, M.H.; Reitsma, M.B.; Sur, P.; Estep, K.; Lee, A.; Marczak, L.; Mokdad, A.H.;
Moradi-Lakeh, M.; et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med. 2017, 377,
13–27.
2. Pan, X.F.; Wang, L.; Pan, A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol. 2021, 9, 373–392.
[CrossRef]
3. Panera, N.; Mandato, C.; Crudele, A.; Bertrando, S.; Vajro, P.; Alisi, A. Genetics, epigenetics and transgenerational transmission of
obesity in children. Front. Endocrinol. 2022, 13, 1006008. [CrossRef] [PubMed]
4. Consales, A.; Morniroli, D.; Vizzari, G.; Mosca, F.; Gianni, M.L. Nutrition for Infant Feeding. Nutrients 2022, 14, 1823. [CrossRef]
5. Zheng, M.; D’Souza, N.J.; Atkins, L.; Ghobadi, S.; Laws, R.; Szymlek-Gay, E.A.; Grimes, C.; Baker, P.; He, Q.Q.; Campbell, K.J.
Breastfeeding and the Longitudinal Changes of Body Mass Index in Childhood and Adulthood: A Systematic Review. Adv. Nutr.
2024, 15, 100152. [CrossRef]
6. Amaro, A.; Baptista, F.I.; Matafome, P. Programming of future generations during breastfeeding: The intricate relation between
metabolic and neurodevelopment disorders. Life Sci. 2022, 298, 120526. [CrossRef] [PubMed]
7. Rzehak, P.; Oddy, W.H.; Mearin, M.L.; Grote, V.; Mori, T.A.; Szajewska, H.; Shamir, R.; Koletzko, S.; Weber, M.; Beilin, L.J.; et al.
Infant feeding and growth trajectory patterns in childhood and body composition in young adulthood. Am. J. Clin. Nutr. 2017,
106, 568–580. [CrossRef] [PubMed]
8. Oddy, W.H.; Mori, T.A.; Huang, R.C.; Marsh, J.A.; Pennell, C.E.; Chivers, P.T.; Hands, B.P.; Jacoby, P.; Rzehak, P.; Koletzko, B.V.;
et al. Early infant feeding and adiposity risk: From infancy to adulthood. Ann. Nutr. Metab. 2014, 64, 262–270. [CrossRef]
9. Trabulsi, J.C.; Smethers, A.D.; Eosso, J.R.; Papas, M.A.; Stallings, V.A.; Mennella, J.A. Impact of early rapid weight gain on odds
for overweight at one year differs between breastfed and formula-fed infants. Pediatr. Obes. 2020, 15, e12688. [CrossRef]
10. Suwaydi, M.A.; Zhou, X.; Perrella, S.L.; Wlodek, M.E.; Lai, C.T.; Gridneva, Z.; Geddes, D.T. The Impact of Gestational Diabetes
Mellitus on Human Milk Metabolic Hormones: A Systematic Review. Nutrients 2022, 14, 3620. [CrossRef]
11. Hui, L.L.; Li, A.M.; Nelson, E.A.S.; Leung, G.M.; Lee, S.L.; Schooling, C.M. In utero exposure to gestational diabetes and adiposity:
Does breastfeeding make a difference? Int. J. Obes. 2018, 42, 1317–1325. [CrossRef]
12. Gunderson, E.P.; Greenspan, L.C.; Faith, M.S.; Hurston, S.R.; Quesenberry, C.P., Jr.; SWIFT Offspring Study Investigators.
Breastfeeding and growth during infancy among offspring of mothers with gestational diabetes mellitus: A prospective cohort
study. Pediatr. Obes. 2018, 13, 492–504. [CrossRef] [PubMed]
13. Dugas, C.; Kearney, M.; Perron, J.; Weisnagel, S.J.; Marc, I.; Robitaille, J. Breastfeeding and growth trajectory from birth to 5 years
among children exposed and unexposed to gestational diabetes mellitus in utero. J. Perinatol. 2021, 41, 1033–1042. [CrossRef]
[PubMed]
14. Aris, I.M.; Soh, S.E.; Tint, M.T.; Saw, S.M.; Rajadurai, V.S.; Godfrey, K.M.; Gluckman, P.D.; Yap, F.; Chong, Y.S.; Lee, Y.S.
Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in
utero. Eur. J. Nutr. 2017, 56, 55–64. [CrossRef] [PubMed]
15. Patro Golab, B.; Santos, S.; Voerman, E.; Lawlor, D.A.; Jaddoe, V.W.V.; Gaillard, R.; MOCO Study Group Authors. Influence of
maternal obesity on the association between common pregnancy complications and risk of childhood obesity: An individual
participant data meta-analysis. Lancet Child Adolesc. Health 2018, 2, 812–821. [CrossRef] [PubMed]
16. Scifres, C.M. Short- and Long-Term Outcomes Associated with Large for Gestational Age Birth Weight. Obstet. Gynecol. Clin. N.
Am. 2021, 48, 325–337. [CrossRef] [PubMed]
17. Jiang, W.; Mo, M.; Si, S.; Wu, J.; Pu, L.; Huang, M.; Shao, B.; Xin, X.; Wang, S.; Shen, Y.; et al. Association of hypertensive disorders
of pregnancy with infant growth in the first 36 months of life. Eur. J. Pediatr. 2022, 181, 133–141. [CrossRef]
18. Peng, Z.; Si, S.; Cheng, H.; Zhou, H.; Chi, P.; Mo, M.; Zhuang, Y.; Liu, H.; Yu, Y. The Associations of Maternal Hemoglobin
Concentration in Different Time Points and Its Changes during Pregnancy with Birth Weight Outcomes. Nutrients 2022, 14, 2542.
[CrossRef] [PubMed]
19. World Health Organization. Indicators for Assessing Infant and Young Child Feeding Practices; World Health Organization: Geneva,
Switzerland, 2008.
20. World Health Organization. Global Strategy for Infant and Young Child Feeding; World Health Organization: Geneva, Switzerland,
2003.
Nutrients 2024, 16, 1351 10 of 11

21. Subgroup, Obstetrics, and Chinese Medical Association Gynecology. Guideline of preconception and prenatal care (2018).
Zhonghua Fu Chan Ke Za Zhi 2018, 53, 7–13.
22. Metzger, B.E.; Gabbe, S.G.; Persson, B.; Lowe, L.P.; Dyer, A.R.; Oats, J.J.N.; Buchanan, T.A. International association of diabetes
and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care
2010, 33, 676–682. [CrossRef]
23. National Health Commission of the People’s Republic of China. Growth Standard for Newborns by Gestational Age; National Health
Commission of the People’s Republic of China: Beijing, China, 2022.
24. Growth Standard for Children under 7 Years of Age. Available online: http://www.nhc.gov.cn/wjw/fyjk/202211/16d8b049fdf5
47978a910911c19bf389.shtml (accessed on 5 February 2024).
25. Pluymen, L.P.M.; Wijga, A.H.; Gehring, U.; Koppelman, G.H.; Smit, H.A.; van Rossem, L. Early introduction of complementary
foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: The PIAMA birth cohort study. Eur. J.
Nutr. 2018, 57, 1985–1993. [CrossRef] [PubMed]
26. Ndirangu, M.N.; Gatimu, S.M.; Mwinyi, H.M.; Kibiwott, D.C. Trends and factors associated with early initiation of breastfeeding
in Namibia: Analysis of the Demographic and Health Surveys 2000–2013. BMC Pregnancy Childbirth 2018, 18, 171. [CrossRef]
[PubMed]
27. Wallenborn, J.T.; Levine, G.A.; Carreira Dos Santos, A.; Grisi, S.; Brentani, A.; Fink, G. Breastfeeding, Physical Growth, and
Cognitive Development. Pediatrics 2021, 147, e2020008029. [CrossRef] [PubMed]
28. Zhou, Q.; Feng, X.L. Breastfeeding practices in Northeast China in 2008 and 2018: Cross-sectional surveys to explore determinants
over a decade. Int. Breastfeed. J. 2023, 18, 25. [CrossRef]
29. Duan, Y.; Yang, Z.; Lai, J.; Yu, D.; Chang, S.; Pang, X.; Jiang, S.; Zhang, H.; Bi, Y.; Wang, J.; et al. Exclusive Breastfeeding Rate
and Complementary Feeding Indicators in China: A National Representative Survey in 2013. Nutrients 2018, 10, 249. [CrossRef]
[PubMed]
30. Kramer, M.S.; Guo, T.; Platt, R.W.; Vanilovich, I.; Sevkovskaya, Z.; Dzikovich, I.; Michaelsen, K.F.; Dewey, K. Feeding effects on
growth during infancy. J. Pediatr. 2004, 145, 600–605. [CrossRef] [PubMed]
31. Griffiths, L.J.; Smeeth, L.; Hawkins, S.S.; Cole, T.J.; Dezateux, C. Effects of infant feeding practice on weight gain from birth to 3
years. Arch. Dis. Child 2009, 94, 577–582. [CrossRef] [PubMed]
32. Gunnarsdottir, I.; Schack-Nielsen, L.; Michaelsen, K.F.; Sorensen, T.I.; Thorsdottir, I. Infant weight gain, duration of exclusive
breast-feeding and childhood BMI—Two similar follow-up cohorts. Public Health Nutr. 2010, 13, 201–207. [CrossRef] [PubMed]
33. Fall, C.H.D.; Kumaran, K. Metabolic programming in early life in humans. Philos. Trans. R. Soc. B Biol. Sci. 2019, 374, 20180123.
[CrossRef]
34. Horta, B.L.; Rollins, N.; Dias, M.S.; Garcez, V.; Perez-Escamilla, R. Systematic review and meta-analysis of breastfeeding and later
overweight or obesity expands on previous study for World Health Organization. Acta Paediatr. 2023, 112, 34–41. [CrossRef]
35. Liu, J.; Gao, D.; Li, Y.; Chen, M.; Wang, X.; Ma, Q.; Ma, T.; Chen, L.; Ma, Y.; Zhang, Y.; et al. Breastfeeding Duration and High
Blood Pressure in Children and Adolescents: Results from a Cross-Sectional Study of Seven Provinces in China. Nutrients 2022,
14, 3152. [CrossRef] [PubMed]
36. Cheng, T.S.; Kwok, M.K.; Leung, G.M.; Schooling, C.M. The Associations of Breast Feeding with Infant Growth and Body Mass
Index to 16 years: ‘Children of 1997’. Paediatr. Perinat. Epidemiol. 2018, 32, 200–209. [CrossRef] [PubMed]
37. Shafer, E.F.; Hawkins, S.S. The Impact of Sex of Child on Breastfeeding in the United States. Matern. Child Health J. 2017, 21,
2114–2121. [CrossRef] [PubMed]
38. Schaefer-Graf, U.M.; Hartmann, R.; Pawliczak, J.; Passow, D.; Abou-Dakn, M.; Vetter, K.; Kordonouri, O. Association of breast-
feeding and early childhood overweight in children from mothers with gestational diabetes mellitus. Diabetes Care 2006, 29,
1105–1107. [CrossRef] [PubMed]
39. Loewenberg Weisband, Y.; Rausch, J.; Kachoria, R.; Gunderson, E.P.; Oza-Frank, R. Hospital Supplementation Differentially
Impacts the Association Between Breastfeeding Intention and Duration Among Women With and Without Gestational Diabetes
Mellitus History. Breastfeed. Med. 2017, 12, 338–344. [CrossRef] [PubMed]
40. Oza-Frank, R.; Moreland, J.J.; McNamara, K.; Geraghty, S.R.; Keim, S.A. Early Lactation and Infant Feeding Practices Differ by
Maternal Gestational Diabetes History. J. Hum. Lact. 2016, 32, 658–665. [CrossRef] [PubMed]
41. Matias, S.L.; Dewey, K.G.; Quesenberry, C.P., Jr.; Gunderson, E.P. Maternal prepregnancy obesity and insulin treatment during
pregnancy are independently associated with delayed lactogenesis in women with recent gestational diabetes mellitus. Am. J.
Clin. Nutr. 2014, 99, 115–121. [CrossRef] [PubMed]
42. Rasmussen, K.M.; Kjolhede, C.L. Prepregnant overweight and obesity diminish the prolactin response to suckling in the first
week postpartum. Pediatrics 2004, 113, e465-71. [CrossRef] [PubMed]
43. Lei, X.; Zhao, D.; Huang, L.; Luo, Z.; Zhang, J.; Yu, X.; Zhang, Y. Childhood Health Outcomes in Term, Large-for-Gestational-Age
Babies With Different Postnatal Growth Patterns. Am. J. Epidemiol. 2018, 187, 507–514. [CrossRef]
44. Viswanathan, S.; McNelis, K.; Makker, K.; Calhoun, D.; Woo, J.G.; Balagopal, B. Childhood obesity and adverse cardiometabolic
risk in large for gestational age infants and potential early preventive strategies: A narrative review. Pediatr. Res. 2022, 92, 653–661.
[CrossRef]
45. Martin, C.R.; Ling, P.R.; Blackburn, G.L. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients
2016, 8, 279. [CrossRef] [PubMed]
Nutrients 2024, 16, 1351 11 of 11

46. Aydin, S. The presence of the peptides apelin, ghrelin and nesfatin-1 in the human breast milk, and the lowering of their levels in
patients with gestational diabetes mellitus. Peptides 2010, 31, 2236–2240. [CrossRef] [PubMed]
47. Yu, X.; Rong, S.S.; Sun, X.; Ding, G.; Wan, W.; Zou, L.; Wu, S.; Li, M.; Wang, D. Associations of breast milk adiponectin, leptin,
insulin and ghrelin with maternal characteristics and early infant growth: A longitudinal study. Br. J. Nutr. 2018, 120, 1380–1387.
[CrossRef] [PubMed]
48. Kaul, P.; Bowker, S.L.; Savu, A.; Yeung, R.O.; Donovan, L.E.; Ryan, E.A. Association between maternal diabetes, being large
for gestational age and breast-feeding on being overweight or obese in childhood. Diabetologia 2019, 62, 249–258. [CrossRef]
[PubMed]
49. Choi, Y.; Nagel, E.M.; Kharoud, H.; Johnson, K.E.; Gallagher, T.; Duncan, K.; Kharbanda, E.O.; Fields, D.A.; Gale, C.A.; Jacobs, K.;
et al. Gestational Diabetes Mellitus Is Associated with Differences in Human Milk Hormone and Cytokine Concentrations in a
Fully Breastfeeding United States Cohort. Nutrients 2022, 14, 667. [CrossRef] [PubMed]
50. Dugas, C.; Perron, J.; Kearney, M.; Mercier, R.; Tchernof, A.; Marc, I.; Weisnagel, S.J.; Robitaille, J. Postnatal Prevention of
Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now? Obes. Facts 2017, 10,
396–406. [CrossRef] [PubMed]
51. Aydin, S.; Geckil, H.; Karatas, F.; Donder, E.; Kumru, S.; Kavak, E.C.; Colak, R.; Ozkan, Y.; Sahin, I. Milk and blood ghrelin level in
diabetics. Nutrition 2007, 23, 807–811. [CrossRef]
52. Li, R.; Scanlon, K.S.; Serdula, M.K. The validity and reliability of maternal recall of breastfeeding practice. Nutr. Rev. 2005, 63,
103–110. [CrossRef]

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