Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months

doi:10.21203/rs.3.rs-4808370/v1

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Research Article

Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months

https://doi.org/10.21203/rs.3.rs-4808370/v1

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Background Limited data are available about the association between feeding strategies and nutritional status of vitamin A (VA) among preterm infants. We aimed to investigate the nutritional status of VA and its association with different feeding strategies among preterm infants aged 3-6 months, and to explore the potential modifying effect of neonatal complications and VA supplementation on the studied association.

Methods We conducted a hospital-based cross-sectional study including 483 preterm infants. Data on feeding strategies, demographic and clinical characteristics were collected from hospital records or through interviews with parents, and serum VA levels were tested among infants aged 3-6 months. Multivariable linear regression and logistic regression were used to evaluate the association of feeding strategies with VA levels and VA deficiency (VAD).

Results The serum VA level (mean±standard deviation [SD]) was 0.25±0.07 mg/L, and the prevalence of VAD was 24.84% among the infants. Compared with exclusive breastfeeding, breast milk plus human milk fortifier, formula, mixed feeding, as well as mixed feeding plus human milk fortifier were respectively associated with a SD increase of VA level in serum (β and 95% confidence interval (CI):1.05 (0.62-1.47), 1.17 (0.99-1.36), 0.52 (0.32-0.72), and 0.97 (0.44-1.49), respectively), and a lower risk of VAD (odds ratio (OR) and 95% CI: 0.14 (0.04-0.47), 0.12 (0.06-0.24), 0.34 (0.19-0.63), and 0.21 (0.05-0.92), respectively). Compared with no formula, term formula, post-discharge preterm formula, and special formula were associated with a SD increase of VA level in serum (β and 95% CI: 0.86 (0.68-1.04), 0.48 (0.21-0.75), and 0.74 (0.42-1.06), respectively) and a lower risk of VAD (OR and 95% CI: 0.20 (0.11-0.36), 0.47 (0.23-0.96), and 0.39 (0.16-0.96), respectively). Neonatal complications modified the associations of feeding regimens or types of formula with VA levels.

Conclusions Feeding with formula and human milk fortifier are associated with better VA status among preterm infants. Healthcare professionals need to be aware of the risk of VAD among preterm infants and the potential for risk reduction through administering formula and human milk fortifier.

Feeding strategies

Preterm infants

Vitamin A

Vitamin A deficiency

Vitamin A (VA) is essential for cell growth, antioxidant capacity and immune function¹. Vitamin A deficiency (VAD) is a significant health concern for children, leading to visual abnormalities, as well as respiratory, digestive diseases, and infectious diseases². Inadequate dietary intake is the primary causes of VAD, which may later lead to visual abnormalities and increased susceptibility to infections in children².

Preterm infants (born at less than 37 completed weeks of gestation) are at higher risk VAD due to limited transfer of VA from the mother during pregnancy and immature intestinal function⁴. It is recommended in China that preterm infants be fed with breast milk until six months of age or later³, supplemented with 1500–2000 IU VA per day for the first three months⁴. Human milk fortifier is recommended for those born < 34 weeks and < 2000g, while term formula or post-discharge preterm formula is used for those born > 34 weeks or > 2000g, depending on their growth and milk intake³. Preterm infants may be given special formula for conditions such as lactose intolerance, indigestion, or milk powder allergy under the guidance of a doctor. Additionally, they should consume food rich in VA when solid foods are introduced at the corrected age of 4–6 months^3–4.

Limited research has investigated the association of feeding strategies, such as feeding regimens and types of formula, with serum VA levels in preterm infants. Previous research has emphasized the importance of maternal VA supplementation during breastfeeding and the introduction of solid food in maintaining adequate VA levels among infants over six months old⁵. However, there is a lack of data for infants under six months old. Considering the high risk of VAD observed in preterm infants and its potential long-term health consequences, it is of public health importance to evaluate the impact of different post-discharge feeding strategies on VA levels in preterm infants. This will provide evidence for the clinical application of VA supplements in preterm infants and early prevention and treatment of VAD.

In this study, we aimed to investigate the association of feeding strategies with serum levels of VA and VAD among preterm infants aged 3–6 months, and to assess the potential modifying effect of neonatal complications and VA supplementation on the studied association.

Study participants

This study utilized data extracted from the "Internet Plus" post-discharge follow-up system for preterm infants, based on the high-risk infants’ management program at the Department of Child Healthcare, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, China. Shenzhen Baoan Women’s and Children’s Hospital is a tertiary grade-A hospital that serves a population of approximately six million. It holds the foremost position among all women’s and children’s hospitals in Shenzhen. This hospital plays a crucial role in providing healthcare services to a large and diverse population, making it an essential institution in the region. This study was approved by the Ethics Committee of the School of Public Health (Shenzhen), Sun Yat-sen University (No. 2024-001). All information was anonymized and de-identified before analysis.

The study population included preterm infants (gestational age < 37^+ 0 weeks) aged 3–6 months who had health check-ups at the Department of Child Healthcare from May 2018 to December 2022. We collected data of 3700 infants and excluded twins (n = 218), infants with major congenital malformation (n = 57), without serum VA tested (n = 2925), or without feeding regimen information (n = 1), and infants with fever, common cold, inflammatory diseases of the central nervous system, respiratory diseases or digestive diseases in the past two weeks (n = 16), leaving 483 preterm infants in the final study. The diagnostic criteria for the aforementioned infant diseases were based on the International Classification of Diseases, 10th edition (ICD-10), with corresponding codes provided in Supplementary Table 1.

Exposure assessment

The exposures of interest were feeding strategies, including feeding regimens, types of formula, intensive feeding, and feeding patterns, collected via interview with parents during health check-ups (Supplementary Table 2). We also collected information on iron supplementation, VA supplementation, vitamin D (VD) supplementation and solid food introduction. Data of solid food introduction were only available in preterm infants at the corrected age of 4–6 months. Corrected age was calculated by subtracting the length of time preterm from the infant’s chronological age at the time of serum VA level test⁶.

Outcomes ascertainment

The outcomes of interest were serum VA levels and VAD among the infants. During health check-ups, 2ml of peripheral venous blood was collected by nurses, and tested at the KingMed Diagnostics Laboratory, Shenzhen, China. Serum VA levels were measured by ultra-high performance liquid chromatography (Agilent 1290 Infinity II). The level of VA was recorded in mg/L. According to the latest diagnostic criteria of the World Health Organization (WHO)⁷ and the Chinese expert consensus on clinical application of VA ⁴, VA levels were further classified into 1) normal (0.30–0.50 mg/L), 2) subclinical deficiency (0.21–0.29 mg/L), 3) deficiency (0.11–0.20 mg/L), and 4) severe deficiency (≤ 0.10mg/L). VAD was defined as serum VA less than 0.20mg/L.

Covariates

We considered potential confounding factors based on previous research, including maternal age at delivery^8–9, gestational complications^10–11, as well as sex¹², gestational age at birth^13–14, birth weight¹³ and age^14–15 during health check-up of the infants. Gestational complications included gestational hypertension, gestational diabetes, and iron deficiency anemia. We also included other maternal characteristics (including parity, mode of delivery, and premature rupture of membrane), neonatal characteristics (including birth length, head circumference at birth, standardized scores of birth length, birth weight and head circumference at birth, and neonatal complications), and infant’s characteristics during health check-up (including length, weight, head circumference, and chronological age). Neonatal complications included asphyxia, respiratory diseases, infection and inflammation-related diseases, neurological diseases and other conditions. Standardized scores for birth measurements were calculated following WHO standards by subtracting the actual measurement from the mean for infants of the same age and sex, and then divided by the standard deviation for infants of the same age and sex.

Statistical analysis

For descriptive analyses, continuous variables were described by mean and standard deviation (SD) as well as median and interquartile range (IQR). Categorical variables were described by frequency and proportion. Analysis of variance (ANOVA) or Welch’s test was used to compare serum VA levels across different feeding strategies and Chi-squared test was used to compare the prevalence of VAD. Linear regression was used to analyze the association between feeding strategies and serum VA levels. Logistic regression was used to analyzed the risk of VAD associated with feeding strategies. In the first model, no covariate was adjusted; in the second model, iron supplement, VA supplement and VD supplement were adjusted; in the third model, maternal age at delivery, gestational complications, and sex, gestational age at birth, birth weight, and age at the time of health check-up of the infant were additionally adjusted.

To assess the potential modifying effect of neonatal complications and VA supplementation on the studied associations, we assessed the interactions between neonatal complications or VA supplementation and feeding strategies by formal test of interaction.

Data management and statistical analyses were conducted by using Stata MP version 17 (Stata Corp LP, College Station, TX, USA). Two-sided P values < 0.05 were considered statistically significant.

Among the 483 preterm infants, the serum VA levels were on average 0.25 ± 0.07 mg/L, and 24.84% (n = 120) had VAD (Table 1). Maternal age at child’s birth was 31.25 ± 4.70 years on average, and 41.61% (n = 201) of mother had gestational complications. Among the infants, the gestational age was 33.59 ± 2.43 weeks and the birth weight was 2135.54 ± 541.13 g. A total of 39.75% (n = 192) of the infants were females. Details of the demographic and clinical characteristics are shown in Table 1 and Supplementary Table 3.

Table 1

Serum VA levels of preterm infants
Nutritional status of VA	N (%)	VA levels (mg/L)
Total	483 (100.00)	0.25 ± 0.07
Normal (0.30–0.50 mg/L)	106 (21.95)	0.35 ± 0.05
Sub-clinical deficiency (0.21–0.29 mg/L)	257 (53.21)	0.24 ± 0.03
Deficiency (0.11–0.20 mg/L)	117 (24.22)	0.17 ± 0.02
Severe deficiency (≤ 0.10 mg/L)	3 (0.62)	0.06 ± 0.03
Abbreviations: VA = vitamin A

Table 2

Demographic and clinical characteristics of preterm infants and their mothers
Characteristics	N (%)	Mean ± SD	Median (P25, P75)
Mothers
Age at delivery (years)		31.25 ± 4.70	31.00 (28.00, 34.00)
≤24	28 (5.80)
25–29	141 (29.19)
30–34	193 (39.96)
≥ 35	106 (21.95)
Unknown	15(3.11)
Gestational complications
No	282 (58.39)
Yes	201 (41.61)
Infants
Sex
Male	291 (60.25)
Female	192 (39.75)
Gestational age at birth (weeks)	483 ^a	33.59 ± 2.43	34.00 (33.00, 36.00)
Birth weight (grams)	483 ^a	2135.54 ± 541.13	2200.00 (1800.00, 2550.00)
Chronological age (months)		4.67 ± 1.30	4.37 (3.40, 6.03)
3	188 (38.92)
4	94 (19.46)
5	63 (13.04)
6	138 (28.57)
Corrected age (months)		3.13 ± 1.47	2.86 (1.90, 4.69)
≤ 1	23 (4.76)
1	115 (23.81)
2	128 (26.50)
3	48 (9.94)
4	92 (19.05)
5	77 (15.94)
Abbreviations: SD = standard deviation ^a Number of infants with information.

Compared with exclusive breastfeeding, all other feeding regimens, particularly formula, were associated with higher serum levels of VA, after multivariable adjustment. Moreover, all formula types, including term formula, post-discharge preterm formula, and special formula, were associated with higher serum levels of VA. As for feeding patterns, both exclusive bottle-feeding and direct breastfeeding plus bottle-feeding were associated with higher serum levels of VA in preterm infants. However, no evidence of difference in VA levels was observed between infants with and without intensive feeding (Table 3). In terms of nutrition supplements, no difference was observed in serum VA levels between infants with and without supplementation of iron, VA or VD, or solid food introduction (Supplementary Table 4).

Table 3

Association between feeding strategies and serum VA levels among preterm infants aged 3–6 months
Feeding strategies	N (%)	VA levels (mg/L)	P ^a	β (95%CI) ^b, per SD	β (95%CI) ^c, per SD	β (95%CI) ^d, per SD
Feeding regimens
Exclusive breastfeeding	182 (37.68)	0.21 ± 0.05	< 0.001	Ref.	Ref.	Ref.
Breast milk plus human milk fortifier	20 (4.14)	0.24 ± 0.07		0.46 (0.04–0.88)	0.42 (-0.00-0.84)	1.05 (0.62–1.47)
Formula	155 (32.09)	0.29 ± 0.08		1.16 (0.96–1.35)	1.16 (0.96–1.35)	1.17 (0.99–1.36)
Mixed feeding	115 (23.81)	0.24 ± 0.06		0.47 (0.25–0.68)	0.46 (0.24–0.67)	0.52 (0.32–0.72)
Mixed feeding plus human milk fortifier	11 (2.28)	0.24 ± 0.05		0.48 (-0.07-1.04)	0.45 (-0.11-1.01)	0.97 (0.44–1.49)
Types of formula
No formula	202 (41.82)	0.21 ± 0.05	< 0.001	Ref.	Ref.	Ref.
Term formula	185 (38.30)	0.28 ± 0.07		0.99 (0.81–1.18)	0.99 (0.81–1.18)	0.86 (0.68–1.04)
Post-discharge preterm formula	60 (12.42)	0.24 ± 0.06		0.31 (0.05–0.58)	0.31 (0.05–0.58)	0.48 (0.21–0.75)
Special formula	36 (7.45)	0.26 ± 0.08		0.64 (0.31–0.97)	0.63 (0.30–0.96)	0.74 (0.42–1.06)
Intensive feeding
No	399 (82.61)	0.25 ± 0.07	0.15	Ref.	Ref.	Ref.
Yes	84 (17.39)	0.24 ± 0.06	0.15	-0.18 (-0.42-0.06)	-0.19 (-0.43-0.06)	0.15 (-0.11-0.41)
Feeding patterns
Exclusive direct breastfeeding	167 (34.58)	0.22 ± 0.05	< 0.001	Ref.	Ref.	Ref.
Exclusive bottle-feeding	198 (40.99)	0.28 ± 0.08		0.91 (0.72–1.11)	0.90 (0.71–1.10)	1.04 (0.85–1.22)
Direct breastfeeding + bottle-feeding	118 (24.43)	0.24 ± 0.06		0.30 (0.08–0.53)	0.30 (0.07–0.52)	0.40 (0.20–0.61)
Abbreviations: VA = vitamin A, CI = confidence interval Mixed feeding: Infant being fed both breast milk and formula Intensive feeding: Infant being fed either breast milk with human milk fortifier or post-discharge preterm formula ^a Analysis of variance (ANOVA) or Welch’s test. ^b Unadjusted model. ^c Adjusted for iron supplementation, VA supplementation, and VD supplementation. ^d Adjusted for iron supplementation, VA supplementation, and VD supplementation, maternal age and gestational complications, and infant’s sex, gestational age at birth, birth weight, chronological age at the time of serum VA test.

We found differences in the risk of VAD among different groups of feeding regimens, types of formula and feeding patterns, but no evidence of difference was observed with intensive feeding (Table 4). Compared with exclusive breastfeeding, breast milk plus human milk fortifier, formula, mixed feeding, as well as mixed feeding plus human milk fortifier were respectively associated with lower risk of VAD. Compared with no formula, different types of formula were all associated with lower risks of VAD. Compared with exclusive direct breastfeeding, exclusive bottle-feeding and direct breastfeeding plus bottle-feeding were also associated with lower risks of VAD. No difference was observed in the risk of VAD between infants with and without iron, VA, or VD supplementation or introduction of solid food (Supplementary Table 5).

Table 4

Association between feeding strategies and the risk of VAD among preterm infants aged 3–6 months
Feeding strategies	VAD		P ^a	OR (95%CI) ^b	OR (95%CI) ^c	OR (95%CI) ^d
Feeding strategies	No (N (%))	Yes (N (%))	P ^a	OR (95%CI) ^b	OR (95%CI) ^c	OR (95%CI) ^d
Feeding regimens
Exclusive breastfeeding	110 (30.30)	72 (60.00)	< 0.001	Ref.	Ref.	Ref.
Breast milk plus human milk fortifier	15 (4.13)	5 (4.17)		0.51 (0.18–1.46)	0.57 (0.20–1.65)	0.14 (0.04–0.47)
Formula	139 (38.29)	16 (13.33)		0.18 (0.10–0.32)	0.17 (0.09–0.31)	0.12 (0.06–0.24)
Mixed feeding	91 (25.07)	24 (20.00)		0.40 (0.24–0.69)	0.43 (0.25–0.73)	0.34 (0.19–0.63)
Mixed feeding plus human milk fortifier	8 (2.20)	3 (2.50)		0.57 (0.15–2.23)	0.65 (0.17–2.54)	0.21 (0.05–0.92)
Types of formula
No formula	125 (34.44)	77 (64.17)	< 0.001	Ref.	Ref.	Ref.
Term formula	168 (46.28)	17 (14.17)		0.16 (0.09–0.29)	0.16 (0.09–0.29)	0.20 (0.11–0.36)
Post-discharge preterm formula	42 (11.57)	18 (15.00)		0.70 (0.37–1.29)	0.71 (0.38–1.33)	0.47 (0.23–0.96)
Special formula	28 (7.71)	8 (6.67)		0.46 (0.20–1.07)	0.47 (0.20–1.09)	0.39 (0.16–0.96)
Intensive feeding
No	304 (83.75)	95 (79.17)	0.25	Ref.	Ref.	Ref.
Yes	59 (16.25)	25 (20.83)	0.25	1.36 (0.81–2.28)	1.43 (0.84–2.42)	0.72 (0.38–1.38)
Feeding patterns
Exclusive direct breastfeeding	103 (28.37)	64 (53.33)	< 0.001	Ref.	Ref.	Ref.
Exclusive bottle-feeding	171 (47.11)	27 (22.50)		0.25 (0.15–0.42)	0.26 (0.15–0.43)	0.14 (0.08–0.27)
Direct breastfeeding plus bottle-feeding	89 (24.52)	29 (24.17)		0.52 (0.31–0.88)	0.55 (0.33–0.93)	0.41 (0.23–0.74)
Abbreviations: VAD = vitamin A deficiency, OR = odds ratio, CI = confidence interval Mixed feeding: Infant being fed both breast milk and formula Intensive feeding: Infant being fed either breast milk with human milk fortifier or post-discharge preterm formula ^a χ² test. ^b Unadjusted model. ^c Adjusted for iron supplementation, VA supplementation, and VD supplementation. ^d Adjusted for iron supplementation, VA supplementation, and VD supplementation, maternal age and gestational complications, and infant’s sex, gestational age at birth, birth weight, chronological age at the time of serum VA test.

Statistical interactions were observed between neonatal complications and feeding regimens and between neonatal complications and types of formula (Supplementary Table 6). Specifically, the higher VA level in relation to breast milk plus human milk fortifier versus exclusive breastfeeding was only observed for infants with neonatal complications, not for infants without neonatal complications. The association between term formula and VA levels was stronger among infants without neonatal complications than those with neonatal complications. No interaction between neonatal complications and feeding regimen or types of formula was found for VAD (Supplementary Table 7). Similarly, we did not observe any evidence of interaction between VA supplementation and feeding regimens or types of formula, for either VA levels or VAD (Supplementary Tables 8 and 9).

In this tertiary-hospital-based study, the average serum level of VA was 0.25 mg/L and the prevalence of VAD was 24.84% among preterm infants aged 3–6 months. We found that compared with exclusive breastfeeding, introduction of formula and human milk fortifier was associated with higher serum levels of VA, and with lower risk of VAD. Compared with no use of formula, any type of formula, including term formula, post-discharge preterm formula, and special formula, was associated with higher serum levels of VA and lower risks of VAD. Neonatal complications modified the association of feeding regimens or type of formula with VA levels.

Our findings showed that compared with other feeding regimens, exclusive breastfeeding was associated with higher risk of VAD in preterm infants. This was consistent with the aforementioned study conducted previously in Shenzhen, China, which showed that the rates of VAD were higher among both infants with exclusive breastfeeding and infants with mixed feeding than those with formula feeding¹⁶. A study from Brazil also showed that breastfeeding infants were considered at risk of VAD¹⁷. As it has been reported that the prevalence of VAD is high among lactating women¹⁸, the low serum VA levels of these mothers might lead to low VA levels in the breastmilk, resulting in high risk of VAD in infants¹⁷. Further research is needed to investigate the association of VA levels in breast milk with the VA levels in infants.

For preterm infants with growth retardation, it is recommended to use human milk fortifier up to the age of 3 months¹⁹. Human milk fortifier provides essential nutrients, including VA, to meet the growth demands of preterm infants²⁰. According to China's national food safety standard (GB25596-2010), human milk fortifier should contain 0.059–0.180 mg VA per 100 kcal. Preterm infants can therefore benefit from breast milk supplemented with human milk fortifier to maintain adequate levels of VA.

Previous research showed that both term formula and post-discharge preterm formula contain higher levels of VA than the concentration of VA in mature breast milk from mothers who delivered preterm infants²¹. Preterm infants often experience feeding intolerance, which can impact nutrient absorption²². Special formulas, such as those with partially hydrolyzed proteins, have been shown to improve the absorption and utilization of VA by reducing digestive burden and enhancing digestive capacity in preterm infants²³. While the amount of VA in bottle-fed milk gradually decreases over time²⁴, our findings support that bottle feeding with human milk fortifier or formula can still provide more sufficient VA than exclusive direct breastfeeding.

In the analysis of statistical interactions, it was found that breast milk combined with human milk fortifier was only associated with higher VA levels among infants with neonatal complications. The well-established benefits of breast milk and breastfeeding for preterm infants have been documented with regard to protection against serious complications^25–26. Given the potential challenges in tolerating high fluid intake, post-discharge feeding for infants with neonatal complications should prioritize dense energy and nutrient provisions, with the addition of fortifiers^27–28. Differently, term formula was associated with increased VA levels in all preterm infants, particularly those without neonatal complications. This could potentially be explained by the possibility that term formula could exert a greater beneficial effect on preterm infants without a history of neonatal complications, as they demonstrated better function related to VA absorption and utilization.

Our findings did not demonstrate an association between VA supplementation and serum VA levels. Additionally, we observed that VA supplementation did not affect the association between feeding strategies and serum VA levels. These results align with previous research indicating a limited impact of VA supplementation on the health outcomes of preterm infants²⁹. Although exclusive breastfeeding and VA supplementation have been widely recommended for infants over 6 months with VAD³⁰, formula feeding might be more effective in preventing or alleviating VAD among younger preterm infants discharged from hospital.

This study addresses a gap in the literature by investigating serum levels of VA in preterm infants. The findings reveal that low VA levels are common in preterm infants aged 3–6 months, thus enhancing our understanding of VA nutritional status among infants. Detailed information on feeding regimens was collected to enable a thorough assessment of feeding for preterm infants. Moreover, a sufficient number of confounders, particularly maternal and birth characteristics, were considered in the regression model, which improved the validity of the findings. However, some limitations should also be acknowledged. As we did not have data of serum VA levels at the time of birth, we were unable to examine the changes of serum VA levels over time. Residual confounding due to unmeasured confounders, such as consumption of animal meat and place of residence⁹, is possible. Additionally, we lacked information on maternal VA supplementation during pregnancy and lactation, which may have an impact on the serum VA level of infants. It should be noted that our results may be limited in generalizability to preterm infants in other areas, as this study was conducted at one tertiary hospital in Shenzhen, China.

In conclusion, VAD is prevalent in preterm infants aged 3–6 months. Compared with exclusive breastfeeding, formula and human milk fortifier feeding were associated with a lower risk of VAD. Moreover, different types of formula were all associated with a higher level of VA than no formula feeding. Healthcare professionals should be aware of the risk of VAD among preterm infants and consider regular monitoring of VA levels and administration of formula and human milk fortifier as potential strategies for lowering this risk during early infancy.

Abbreviations and acronyms	Expansion
VA	Vitamin A
VAD	Vitamin A Deficiency
CI	Confidence Interval
OR	Odds Ratio
WHO	World Health Organization

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the School of Public Health (Shenzhen), Sun Yat-sen University (No. 2024-001). Informed consent was waived due to the retrospective study design.

Consent for publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are not publicly available due to privacy concern and ethical restrictions.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the 100 Talents Plan Foundation of Sun Yat-sen University (RC) [grant number No. 58000-12230022]; the Guangdong Basic and Applied Basic Research Fund (RC) [grant number No. 2022A1515110417]; and the Shenzhen Science and Technology Innovation Program (LM) [grant number No. JCYJ201908809183601667]. The funders had no role in study design, data collection, analysis, drafting of the manuscript or publication process.

Authors' contributions

All authors had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. They are the guarantors. LM and RC conceived and designed the experiments. BL, WC (Cao) and WC (Chen) analysed the data. BL, WC (Cao) and WC (Chen) wrote the first draft of the manuscript. All authors contributed to the writing of the manuscript, interpreted the data, critically revised the manuscript for important intellectual content and agreed to be accountable for all aspects of the work. LM and RC obtained funding and provided administrative, technical, and material support. All authors read and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Acknowledgements

Not applicable.

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Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months

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Abstract

Introduction

Patients and methods

Study participants

Exposure assessment

Outcomes ascertainment

Covariates

Statistical analysis

Results

Discussion

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References

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Supplementary Files

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