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

Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months Boyu Li, Wei Cao, Wen Chen, Feng Wu, Qian Lv, Bilan Ding, Luanxun Lin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4808370/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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 Introduction Vitamin A (VA) is essential for cell growth, antioxidant capacity and immune function 1 . Vitamin A deficiency (VAD) is a significant health concern for children, leading to visual abnormalities, as well as respiratory, digestive diseases, and infectious diseases 2 . Inadequate dietary intake is the primary causes of VAD, which may later lead to visual abnormalities and increased susceptibility to infections in children 2 . 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 function 4 . It is recommended in China that preterm infants be fed with breast milk until six months of age or later 3 , supplemented with 1500–2000 IU VA per day for the first three months 4 . Human milk fortifier is recommended for those born < 34 weeks and 34 weeks or > 2000g, depending on their growth and milk intake 3 . 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 old 5 . 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. Patients and methods 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 test 6 . 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 sex 12 , gestational age at birth 13 – 14 , birth weight 13 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. Results 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 -0.18 (-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 No (N (%)) Yes (N (%)) 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) 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 χ 2 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). Discussion 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 feeding 16 . A study from Brazil also showed that breastfeeding infants were considered at risk of VAD 17 . As it has been reported that the prevalence of VAD is high among lactating women 18 , the low serum VA levels of these mothers might lead to low VA levels in the breastmilk, resulting in high risk of VAD in infants 17 . 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 months 19 . Human milk fortifier provides essential nutrients, including VA, to meet the growth demands of preterm infants 20 . 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 infants 21 . Preterm infants often experience feeding intolerance, which can impact nutrient absorption 22 . 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 infants 23 . While the amount of VA in bottle-fed milk gradually decreases over time 24 , 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 infants 29 . Although exclusive breastfeeding and VA supplementation have been widely recommended for infants over 6 months with VAD 30 , 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 residence 9 , 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. The list of abbreviations and acronyms Abbreviations and acronyms Expansion VA Vitamin A VAD Vitamin A Deficiency CI Confidence Interval OR Odds Ratio WHO World Health Organization Declarations 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. References Carazo A, Macáková K, Matoušová K, Krčmová LK, Protti M, Mladěnka P, Vitamin A, Update. Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity. Nutrients. 2021;13(5):1703. WHO. Global prevalence of vitamin A deficiency in populations at risk 1995–2005: WHO global database on vitamin A deficiency. 1 st ed. Geneva: WHO; 2009. China Preventive Medicine Association. 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Vitamin A concentration in human milk and its relationship with liver reserve formation and compliance with the recommended daily intake of vitamin A in pre-term and term infants in exclusive breastfeeding. Arch Gynecol Obstet. 2015;291(2):319–25. Katz J, Khatry SK, West KP, Humphrey JH, Leclerq SC, Kimbrough E, et al. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J Nutr. 1995;125(8):2122–27. Haiden N, Haschke F. New Ways to Provide a Human Milk Fortifier during Breastfeeding. Nestle Nutr Inst Workshop Ser 2021; 96101–06. Arslanoglu S, Boquien CY, King C, Lamireau D, Tonetto P, Barnett D et al. Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification. Front Pediatr 2019; 776. Hanson C, Lyden E, Furtado J, Van Ormer M, Anderson-Berry A. A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas. Nutrients. 2016;8(11):681. Senterre T, Rigo J. Hydrolyzed Proteins in Preterm Infants. Nestle Nutr Inst Workshop Ser 2016; 8639–49. Vandenplas Y, Salvatore S. Infant Formula with Partially Hydrolyzed Proteins in Functional Gastrointestinal Disorders. In: Bhatia J, Shamir R, Vandenplas Y, ^editors, editors. Protein in Neonatal and Infant Nutrition: Recent Updates: 86th Nestlé Nutrition Institute Workshop. Beijing, May 2015: S.Karger AG; 2016. p. 0. Francis J, Rogers K, Dickton D, Twedt R, Pardini R. Decreasing retinol and α-tocopherol concentrations in human milk and infant formula using varied bottle systems. Matern Child Nutr. 2012;8(2):215–24. Cheong J, Burnett AC, Treyvaud K, Spittle AJ. Early environment and long-term outcomes of preterm infants. J Neural Transm (Vienna). 2020;127(1):1–08. Christian P, Mullany LC, Hurley KM, Katz J, Black RE. Nutrition and maternal, neonatal, and child health. Semin Perinatol. 2015;39(5):361–72. Guimarães H, Rocha G, Guedes MB, Guerra P, Silva AI, Pissarra S. Nutrition of preterm infants with bronchopulmonary dysplasia after hospital discharge – Part I. J Pediatr Neonatal Individualized Med (JPNIM). 2014;3(1):e30116. Rocha G, Guimarães H, Pereira-da-Silva L. The Role of Nutrition in the Prevention and Management of Bronchopulmonary Dysplasia: A Literature Review and Clinical Approach. Int J Environ Res Public Health. 2021;18(12):200–08. Uberos J, Miras-Baldo M, Jerez-Calero A, Narbona-López E. Effectiveness of vitamin A in the prevention of complications of prematurity. Pediatr Neonatol. 2014;55(5):358–62. Lassi ZS, Mallick D, Das JK, Mal L, Salam RA, Bhutta ZA. Essential interventions for child health. Reprod Health. 2014;11(Suppl 1):S4. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4808370","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":334202819,"identity":"6ceb3acf-be1f-4811-abe1-9d98cb6ae15e","order_by":0,"name":"Boyu Li","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Boyu","middleName":"","lastName":"Li","suffix":""},{"id":334202822,"identity":"a7caeadc-c67e-4778-a604-f88527a28082","order_by":1,"name":"Wei Cao","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Cao","suffix":""},{"id":334202823,"identity":"c21331dd-bf5e-44f8-8647-61d93a5bc5b2","order_by":2,"name":"Wen Chen","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Chen","suffix":""},{"id":334202824,"identity":"5e60a5a8-fdd1-4c9b-928f-5aa9a419a922","order_by":3,"name":"Feng Wu","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Wu","suffix":""},{"id":334202825,"identity":"7f6a4562-8cf2-49f5-8fe9-5840ab3488b2","order_by":4,"name":"Qian Lv","email":"","orcid":"","institution":"Shenzhen Baoan Women’s and Children’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Lv","suffix":""},{"id":334202828,"identity":"e838862a-c4ff-42fa-966d-988ce742270c","order_by":5,"name":"Bilan Ding","email":"","orcid":"","institution":"Shenzhen Baoan Women’s and Children’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bilan","middleName":"","lastName":"Ding","suffix":""},{"id":334202834,"identity":"e0c8fb03-4da0-454a-b1c2-f970bd6b5b96","order_by":6,"name":"Luanxun Lin","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Luanxun","middleName":"","lastName":"Lin","suffix":""},{"id":334202836,"identity":"3ed4bd76-b7e6-4dc3-972d-5af2187e6d9f","order_by":7,"name":"Liya Ma","email":"","orcid":"","institution":"Shenzhen Baoan Women’s and Children’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liya","middleName":"","lastName":"Ma","suffix":""},{"id":334202840,"identity":"ccad516d-ea1e-4f62-8d4d-9eb381297d0e","order_by":8,"name":"Ruoqing Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYDACCTBpI8cPJA88gInyENaSZizZANSSQIKWw4kbDgAporTwz24+9riijNnY+Nrhh0Bb6hLnz0hgfPC2jUHeHJcld46lG545xyZndjvNAKgFaN2NBGbDuW0MhjsbsGsxkMgxk2xs4zE2u50A0nIgcYNEAps0bxsDkItLS/43oBaJxM2z0z/AHMb+G7+WHDagFoPEDdI5IFuYExtuJLAx49MicSPNTLLhXIKxxO2cggMJBoeNN5x52Cw555yE4QYcWvhnJD+TbCj7L8c/O33zhw8VdbLz25MPfnhTZiOPyxYIYIO7k8GxgYGxgQEWX0RoYWCwJ6B0FIyCUTAKRiAAAAq3XkSxrOvvAAAAAElFTkSuQmCC","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ruoqing","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-07-26 13:22:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4808370/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4808370/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80796920,"identity":"8d9de763-f35b-40c8-ac40-250f6974dba1","added_by":"auto","created_at":"2025-04-17 07:47:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1118992,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4808370/v1/2cb7b601-f090-4e0e-b338-e130c8f1670f.pdf"},{"id":63392777,"identity":"36845f65-c222-4782-a663-fbb3e3d22a07","added_by":"auto","created_at":"2024-08-27 16:07:16","extension":"xls","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":79872,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial20240726.xls","url":"https://assets-eu.researchsquare.com/files/rs-4808370/v1/47ef3212e1aebf4bfde05f3e.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVitamin A (VA) is essential for cell growth, antioxidant capacity and immune function\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Vitamin A deficiency (VAD) is a significant health concern for children, leading to visual abnormalities, as well as respiratory, digestive diseases, and infectious diseases\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Inadequate dietary intake is the primary causes of VAD, which may later lead to visual abnormalities and increased susceptibility to infections in children\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePreterm 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 function\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. It is recommended in China that preterm infants be fed with breast milk until six months of age or later\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, supplemented with 1500\u0026ndash;2000 IU VA per day for the first three months\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Human milk fortifier is recommended for those born\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks and \u0026lt;\u0026thinsp;2000g, while term formula or post-discharge preterm formula is used for those born\u0026thinsp;\u0026gt;\u0026thinsp;34 weeks or \u0026gt;\u0026thinsp;2000g, depending on their growth and milk intake\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. 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\u0026ndash;6 months\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLimited 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 old\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. 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.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to investigate the association of feeding strategies with serum levels of VA and VAD among preterm infants aged 3\u0026ndash;6 months, and to assess the potential modifying effect of neonatal complications and VA supplementation on the studied association.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy participants\u003c/h2\u003e \u003cp\u003eThis study utilized data extracted from the \"Internet Plus\" post-discharge follow-up system for preterm infants, based on the high-risk infants\u0026rsquo; management program at the Department of Child Healthcare, Shenzhen Baoan Women\u0026rsquo;s and Children\u0026rsquo;s Hospital, Shenzhen, China. Shenzhen Baoan Women\u0026rsquo;s and Children\u0026rsquo;s Hospital is a tertiary grade-A hospital that serves a population of approximately six million. It holds the foremost position among all women\u0026rsquo;s and children\u0026rsquo;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.\u003c/p\u003e \u003cp\u003eThe study population included preterm infants (gestational age\u0026thinsp;\u0026lt;\u0026thinsp;37\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e weeks) aged 3\u0026ndash;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\u0026thinsp;=\u0026thinsp;218), infants with major congenital malformation (n\u0026thinsp;=\u0026thinsp;57), without serum VA tested (n\u0026thinsp;=\u0026thinsp;2925), or without feeding regimen information (n\u0026thinsp;=\u0026thinsp;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\u0026thinsp;=\u0026thinsp;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\u0026nbsp;1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExposure assessment\u003c/h2\u003e \u003cp\u003e 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\u0026nbsp;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\u0026ndash;6 months. Corrected age was calculated by subtracting the length of time preterm from the infant\u0026rsquo;s chronological age at the time of serum VA level test\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes ascertainment\u003c/h2\u003e \u003cp\u003eThe 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)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e and the Chinese expert consensus on clinical application of VA \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e, VA levels were further classified into 1) normal (0.30\u0026ndash;0.50 mg/L), 2) subclinical deficiency (0.21\u0026ndash;0.29 mg/L), 3) deficiency (0.11\u0026ndash;0.20 mg/L), and 4) severe deficiency (\u0026le;\u0026thinsp;0.10mg/L). VAD was defined as serum VA less than 0.20mg/L.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCovariates\u003c/h2\u003e \u003cp\u003eWe considered potential confounding factors based on previous research, including maternal age at delivery\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, gestational complications\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, as well as sex\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, gestational age at birth\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, birth weight\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e and age\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e 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\u0026rsquo;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.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor 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\u0026rsquo;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.\u003c/p\u003e \u003cp\u003eTo 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.\u003c/p\u003e \u003cp\u003eData management and statistical analyses were conducted by using Stata MP version 17 (Stata Corp LP, College Station, TX, USA). Two-sided \u003cem\u003eP\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 483 preterm infants, the serum VA levels were on average 0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 mg/L, and 24.84% (n\u0026thinsp;=\u0026thinsp;120) had VAD (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Maternal age at child\u0026rsquo;s birth was 31.25\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70 years on average, and 41.61% (n\u0026thinsp;=\u0026thinsp;201) of mother had gestational complications. Among the infants, the gestational age was 33.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43 weeks and the birth weight was 2135.54\u0026thinsp;\u0026plusmn;\u0026thinsp;541.13 g. A total of 39.75% (n\u0026thinsp;=\u0026thinsp;192) of the infants were females. Details of the demographic and clinical characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Supplementary Table\u0026nbsp;3.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSerum VA levels of preterm infants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNutritional status of VA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVA levels (mg/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e483 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal (0.30\u0026ndash;0.50 mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106 (21.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSub-clinical deficiency (0.21\u0026ndash;0.29 mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e257 (53.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeficiency (0.11\u0026ndash;0.20 mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e117 (24.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere deficiency (\u0026le;\u0026thinsp;0.10 mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbbreviations: VA\u0026thinsp;=\u0026thinsp;vitamin A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of preterm infants and their mothers\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMedian (P25, P75)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMothers\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at delivery (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.25\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.00 (28.00, 34.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (5.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ndash;29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141 (29.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e193 (39.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (21.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e282 (58.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e201 (41.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfants\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e291 (60.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192 (39.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational age at birth (weeks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e483 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.00 (33.00, 36.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth weight (grams)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e483 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2135.54\u0026thinsp;\u0026plusmn;\u0026thinsp;541.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2200.00 (1800.00, 2550.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronological age (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.37 (3.40, 6.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188 (38.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (19.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (13.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138 (28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCorrected age (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.86 (1.90, 4.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (4.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (23.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (26.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (9.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (15.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: SD\u0026thinsp;=\u0026thinsp;standard deviation\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Number of infants with information.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCompared 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\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). 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\u0026nbsp;4).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between feeding strategies and serum VA levels among preterm infants aged 3\u0026ndash;6 months\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeding strategies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVA levels (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eβ\u003c/em\u003e (95%CI) \u003csup\u003eb\u003c/sup\u003e,\u003c/p\u003e \u003cp\u003eper SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eβ\u003c/em\u003e (95%CI) \u003csup\u003ec\u003c/sup\u003e,\u003c/p\u003e \u003cp\u003eper SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eβ\u003c/em\u003e (95%CI) \u003csup\u003ed\u003c/sup\u003e,\u003c/p\u003e \u003cp\u003eper SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeding regimens\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e182 (37.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast milk plus human milk fortifier\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (4.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46 (0.04\u0026ndash;0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.42 (-0.00-0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.05 (0.62\u0026ndash;1.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155 (32.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.16 (0.96\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.16 (0.96\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.17 (0.99\u0026ndash;1.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (23.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.47 (0.25\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.46 (0.24\u0026ndash;0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.52 (0.32\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding plus human milk fortifier\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48 (-0.07-1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.45 (-0.11-1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.97 (0.44\u0026ndash;1.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of formula\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202 (41.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e185 (38.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99 (0.81\u0026ndash;1.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99 (0.81\u0026ndash;1.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.86 (0.68\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-discharge preterm formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (12.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.31 (0.05\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.31 (0.05\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.48 (0.21\u0026ndash;0.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecial formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (7.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.64 (0.31\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.63 (0.30\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.74 (0.42\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntensive feeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e399 (82.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (17.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.18 (-0.42-0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.19 (-0.43-0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.15 (-0.11-0.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFeeding patterns\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive direct breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e167 (34.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive bottle-feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198 (40.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.91 (0.72\u0026ndash;1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.90 (0.71\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.04 (0.85\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDirect breastfeeding\u0026thinsp;+\u0026thinsp;bottle-feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (24.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.30 (0.08\u0026ndash;0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.30 (0.07\u0026ndash;0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.40 (0.20\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: VA\u0026thinsp;=\u0026thinsp;vitamin A, CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/p\u003e \u003cp\u003eMixed feeding: Infant being fed both breast milk and formula\u003c/p\u003e \u003cp\u003eIntensive feeding: Infant being fed either breast milk with human milk fortifier or post-discharge preterm formula\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Analysis of variance (ANOVA) or Welch\u0026rsquo;s test.\u003c/p\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Unadjusted model.\u003c/p\u003e \u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Adjusted for iron supplementation, VA supplementation, and VD supplementation.\u003c/p\u003e \u003cp\u003e\u003csup\u003ed\u003c/sup\u003e Adjusted for iron supplementation, VA supplementation, and VD supplementation, maternal age and gestational complications, and infant\u0026rsquo;s sex, gestational age at birth, birth weight, chronological age at the time of serum VA test.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe 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\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). 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\u0026nbsp;5).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between feeding strategies and the risk of VAD among preterm infants aged 3\u0026ndash;6 months\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFeeding strategies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eVAD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR (95%CI) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR (95%CI) \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR (95%CI) \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (N (%))\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes (N (%))\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeding regimens\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110 (30.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast milk plus human milk fortifier\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (4.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51 (0.18\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57 (0.20\u0026ndash;1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.14 (0.04\u0026ndash;0.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (38.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (13.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18 (0.10\u0026ndash;0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.17 (0.09\u0026ndash;0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.12 (0.06\u0026ndash;0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (25.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (20.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.40 (0.24\u0026ndash;0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.43 (0.25\u0026ndash;0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.34 (0.19\u0026ndash;0.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding plus human milk fortifier\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57 (0.15\u0026ndash;2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.65 (0.17\u0026ndash;2.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.21 (0.05\u0026ndash;0.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of formula\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125 (34.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (64.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTerm formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168 (46.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (14.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16 (0.09\u0026ndash;0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16 (0.09\u0026ndash;0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.20 (0.11\u0026ndash;0.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-discharge preterm formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (11.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.70 (0.37\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.71 (0.38\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.47 (0.23\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecial formula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (7.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46 (0.20\u0026ndash;1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.47 (0.20\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.39 (0.16\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntensive feeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e304 (83.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 (79.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (16.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (20.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.36 (0.81\u0026ndash;2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.43 (0.84\u0026ndash;2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.72 (0.38\u0026ndash;1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFeeding patterns\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive direct breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (28.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (53.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusive bottle-feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e171 (47.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (22.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25 (0.15\u0026ndash;0.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.26 (0.15\u0026ndash;0.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.14 (0.08\u0026ndash;0.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDirect breastfeeding plus bottle-feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (24.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (24.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.52 (0.31\u0026ndash;0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55 (0.33\u0026ndash;0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.41 (0.23\u0026ndash;0.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: VAD\u0026thinsp;=\u0026thinsp;vitamin A deficiency, OR\u0026thinsp;=\u0026thinsp;odds ratio, CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/p\u003e \u003cp\u003eMixed feeding: Infant being fed both breast milk and formula\u003c/p\u003e \u003cp\u003eIntensive feeding: Infant being fed either breast milk with human milk fortifier or post-discharge preterm formula\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e χ\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e test.\u003c/p\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Unadjusted model.\u003c/p\u003e \u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Adjusted for iron supplementation, VA supplementation, and VD supplementation.\u003c/p\u003e \u003cp\u003e\u003csup\u003ed\u003c/sup\u003e Adjusted for iron supplementation, VA supplementation, and VD supplementation, maternal age and gestational complications, and infant\u0026rsquo;s sex, gestational age at birth, birth weight, chronological age at the time of serum VA test.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eStatistical interactions were observed between neonatal complications and feeding regimens and between neonatal complications and types of formula (Supplementary Table\u0026nbsp;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\u0026nbsp;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\u0026nbsp;8 and 9).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn 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\u0026ndash;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.\u003c/p\u003e \u003cp\u003eOur 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 feeding\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. A study from Brazil also showed that breastfeeding infants were considered at risk of VAD\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. As it has been reported that the prevalence of VAD is high among lactating women\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, the low serum VA levels of these mothers might lead to low VA levels in the breastmilk, resulting in high risk of VAD in infants\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Further research is needed to investigate the association of VA levels in breast milk with the VA levels in infants.\u003c/p\u003e \u003cp\u003eFor preterm infants with growth retardation, it is recommended to use human milk fortifier up to the age of 3 months\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Human milk fortifier provides essential nutrients, including VA, to meet the growth demands of preterm infants\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. According to China's national food safety standard (GB25596-2010), human milk fortifier should contain 0.059\u0026ndash;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.\u003c/p\u003e \u003cp\u003ePrevious 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 infants\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Preterm infants often experience feeding intolerance, which can impact nutrient absorption\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. 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 infants\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. While the amount of VA in bottle-fed milk gradually decreases over time\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, our findings support that bottle feeding with human milk fortifier or formula can still provide more sufficient VA than exclusive direct breastfeeding.\u003c/p\u003e \u003cp\u003eIn 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\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. 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.\u003c/p\u003e \u003cp\u003eOur 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 infants\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Although exclusive breastfeeding and VA supplementation have been widely recommended for infants over 6 months with VAD\u003csup\u003e30\u003c/sup\u003e, formula feeding might be more effective in preventing or alleviating VAD among younger preterm infants discharged from hospital.\u003c/p\u003e \u003cp\u003eThis 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\u0026ndash;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 residence\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, 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.\u003c/p\u003e \u003cp\u003eIn conclusion, VAD is prevalent in preterm infants aged 3\u0026ndash;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.\u003c/p\u003e"},{"header":"The list of abbreviations and acronyms","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations and acronyms\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpansion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eVitamin A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eVAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eVitamin A Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eWHO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eWorld Health Organization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not publicly available due to privacy concern and ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCarazo A, Mac\u0026aacute;kov\u0026aacute; K, Matoušov\u0026aacute; K, Krčmov\u0026aacute; LK, Protti M, Mladěnka P, Vitamin A, Update. Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity. Nutrients. 2021;13(5):1703.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO. Global prevalence of vitamin A deficiency in populations at risk 1995\u0026ndash;2005: WHO global database on vitamin A deficiency. 1 st ed. Geneva: WHO; 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChina Preventive Medicine Association. Society of Child Health. 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BMJ 2010; 340c1101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKositamongkol S, Suthutvoravut U, Chongviriyaphan N, Feungpean B, Nuntnarumit P. Vitamin A and E status in very low birth weight infants. J Perinatol. 2011;31(7):471\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlint A, New K, Davies MW. Cup feeding versus other forms of supplemental enteral feeding for newborn infants unable to fully breastfeed. Cochrane Database Syst Rev. 2016; 2016(8): CD5092.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Academies of Sciences, Engineering, and Medicine, Medicine HA, Division, Board FAN, for, Age COSE. FRFI. Feeding Infants and Children from Birth to 24 Months: Summarizing Existing Guidance. 1 st ed. Washington (DC): National Academies Press (US); 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi H, Wang W, Qian G, Ren L, Feng X. Study on influencing factors of vitamin A deficiency in 6-month-old infants. Chin J Woman Child Health Res. 2021;32(03):410\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSouza G, Dolinsky M, Matos A, Chagas C, Ramalho A. Vitamin A concentration in human milk and its relationship with liver reserve formation and compliance with the recommended daily intake of vitamin A in pre-term and term infants in exclusive breastfeeding. Arch Gynecol Obstet. 2015;291(2):319\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatz J, Khatry SK, West KP, Humphrey JH, Leclerq SC, Kimbrough E, et al. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J Nutr. 1995;125(8):2122\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaiden N, Haschke F. New Ways to Provide a Human Milk Fortifier during Breastfeeding. 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Pediatr Neonatol. 2014;55(5):358\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLassi ZS, Mallick D, Das JK, Mal L, Salam RA, Bhutta ZA. Essential interventions for child health. Reprod Health. 2014;11(Suppl 1):S4.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Feeding strategies, Preterm infants, Vitamin A, Vitamin A deficiency","lastPublishedDoi":"10.21203/rs.3.rs-4808370/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4808370/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eLimited 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e 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).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e 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.\u003c/p\u003e","manuscriptTitle":"Impact of feeding strategies on serum vitamin A levels in preterm infants aged 3-6 months","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-27 16:07:11","doi":"10.21203/rs.3.rs-4808370/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"acbf7fed-7f8b-4759-85b2-34c354e43b5f","owner":[],"postedDate":"August 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-17T07:39:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-27 16:07:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4808370","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4808370","identity":"rs-4808370","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}