Study selection

The initial search for all the potential SRs from the databases returned 1015 records, of which 861 remained after removing duplicates. Through title screening and abstract reading, 74 records were kept for full-text reading assessment. There were further 57 articles excluded for the following reasons: (1) intervention did not meet the inclusion criteria; (2) topic duplication; and (3) there was no meta-analysis of the outcomes. Altogether, 17 eligible SRs met the inclusion criteria of this review. The study selection process is reflected in Fig. 1.

Fig. 1
figure1

The flow diagram of study selection

Characteristic of included studies

In total, 161 quantitative primary studies were synthesized in the 17 SRs, all of which were RCTs or quasi-RCTs. Nine SRs [3, 14,15,16,17,18,19,20,21] were published in the late 3 years (2018–2020), 5 SRs [22,23,24,25,26] were between year 2016 to year 2017 and only 3 SRs [27,28,29] were from year 2007, year 2013 and year 2014. Fourteen SRs [3, 14, 15, 17, 19,20,21,22,23, 25,26,27,28,29] were Cochrane SRs and 3 SRs [16, 18, 24] were conventional ones. As for the number of studies included, only 6 SRs [14, 16, 24,25,26,27] incorporated more than 10 primary studies with a relatively larger sample size. Considering the different health outcome assessments, some SRs [16, 17, 24, 27] focused on the same interventions, and all were included to better observe the effect. The characteristics of all the included SRs are summarized in Table 1.

Table 1 Characteristic of the included studies

Methodological quality of included SRs according to AMSTAR

The results of the quality assessment according to AMSTAR tool are shown in Table 2. All the SRs were of high quality indicated that the methodological quality of most of the included systematic reviews was generally of sufficient standard. 2 SRs [14, 26] scoring 11, 10 SRs [3, 15, 17, 20, 22, 24, 25, 27,28,29] scoring 10, 3 SRs [16, 19, 21] scoring 9 and 2 SRs [18, 23] scoring 8. All the SRs met the AMSTAR criteria 1 (prior design provided), criteria 2 (duplicate study selection and data extraction), criteria 6 (characteristics of the included studies provided), criteria 7 (scientific quality of the included studies assessed and documented), and criteria 8 (scientific quality of the included studies used appropriately in formulating conclusions). The least SR met AMSTAR criteria was 10 (likelihood of publication bias assessed) owing to the small number of the primary quantitative studies included in several SRs [3, 15, 17, 19,20,21,22,23, 25, 27,28,29].

Table 2 Methodological quality assessment of included studies according to the AMSTAR tool

Effectiveness of the interventions on health outcomes and quality of evidence

The effectiveness of the interventions on specific health outcomes of the included systematic reviews are presented in Table 3. Overall, the systematic reviews identified a total of 17 independent randomized trails investigating the use of feeding supplementation to promote growth development and reduce incidence of disease on preterm infants. A total of 15 kinds of different nutrient supplementation for the feeding of preterm infants were summarized in this review. The feeding supplementation could be classified into seven categories: protein (protein, lactoferrin), carbohydrate (prebiotic, inositol), fat (fat, LCPUFA), amino acid (arginine, glutamine), mineral (calcium), vitamin (vitamin D), and others (iodine, multi-nutrient, and probiotic).

Table 3 Characteristic of interventions

Regarding the overall effectiveness of feeding supplementation on health outcomes, fourteen SRs [3, 14, 16,17,18, 20,21,22, 24,25,26,27,28,29] concluded that 12 substances were associated with health improvement as a result of the extra supplementation in breast milk or formula. They were lactoferrin, inositol, prebiotics, protein, carbohydrate, vitamin D, arginine, glutamine, LCPUFA, multi-nutrient, taurine, and probiotics which were added to the feeding of preterm infants at a particular dose. Three SRs [15, 19, 23] reported no effect of the supplements of iodine, fat, calcium and phosphorus on the preterm infants due to there was no statistical significance.

Given that different outcomes were reported in each SR, as shown in Table 3, the specific outcomes improved by feeding supplementation were classified into six aspects: physical growth, neurodevelopment, biochemical outcome, other health outcomes, morbidity, and all-cause mortality. And the quality of statistically significant evidences according to GRADE rating was shown in Table 4.

Table 4 Evidence quality assessment of according to the GRADE guidelines

Physical growth

The effectiveness of feeding supplementation on physical growth was assessed by twelve SRs provided results of meta-analysis. [15, 18,19,20,21,22,23, 25,26,27,28,29]. All included SRs were deemed of high quality.

Four SRs [18, 20, 21, 25] concluded that there were effects to physical growth improvement as a result of the extra supplementation in breast milk or formula.

Yang et al. [18] concluded that high dose Vitamin D feeding on preterm infants, length gain and head circumference gain were increased at short term, There was a high certainty of evidence according to the GRADE rating. Amissah et al. [20] concluded that protein supplementation in preterm feeding promotes growth in a short period of time. There was a low certainty of evidence according to the GRADE rating. Amissah et al. [21] concluded that prebiotics supplementation of human milk may increase in weight at short term. There was a very low certainty of evidence according to the GRADE rating. Moon et al. [25] concluded that LCPUFA supplementation in preterm infants promote weigh gain and length gain. There was a low certainty of evidence according to the GRADE rating.

Eight SRs [15, 19, 22, 23, 26,27,28,29] concluded that additional feeding supplementation on preterm infants not definite had an influence.

Neurodevelopment

The effectiveness of feeding supplementation on neurodevelopment was assessed by eight SRs provided results of meta-analysis. [14, 15, 22, 25,26,27,28,29]. All included SRs were deemed of high quality.

In long term, the effectiveness of feeding supplements of Lactoferrin, Iodine, Arginine, glutamine, LCPUFA, Probiotics and taurine on neurodevelopment all reported no statistical significance. [14, 15, 22, 25,26,27] Meantime, in short term, the effectiveness of feeding supplements of taurine was no statistical significance [29].

However, Young et al. [28] concluded a promotion effect of mult-inutrient supplement on Visual acuity. There was a low certainty of evidence according to the GRADE rating.

Biochemical outcomes

The effectiveness of feeding supplementation on biochemical outcomes was assessed by five SRs provided results of meta-analysis [15, 17, 18, 20, 23]. All included SRs were deemed of high quality.

Two SRs [18, 20] concluded that nutritional supplements had an impact on biochemical outcomes. Yang et al. [18] concluded Vitamin D supplementation in preterm infants increased Ig-A, Ig-G and IL-12 levels. The level of evidence quality was high, low and moderate respectively according to the GRADE rating.

Amissah et al. [20] compared to those who received no additional protein, these infants observed blood urea nitrogen increased. There was a low certainty of evidence according to the GRADE rating.

Meanwhile, there were three SRs [15, 17, 23] concluded that the feeding supplementation of iodine, prebiotics, calcium and/or phosphorus was not effective on biochemical outcomes.

Other health outcomes

The effectiveness of feeding supplementation on other health outcomes was assessed by twelve SRs provided results of meta-analysis [14,15,16,17, 19,20,21, 23, 26,27,28,29]. All included SRs were deemed of high quality.

Nine SRs [14, 16, 17, 20, 21, 26,27,28,29] concluded that the additional feeding supplementation on preterm infants have an influence on other health outcomes. Pammi et al. [14] reported the length of hospital stay and urinary tract infection were both decreased. There was a low certainty of evidence according to the GRADE rating. Chi et al. [16] showed that the use of prebiotics with preterm infants reduced time to achieve full enteral feeding and hospital stay, and increased the stool frequency. The quality of evidence according to the GRADE rating were very low, very low and low certainty. Armannia et al. [17] reported that phototherapy rate and hospital stay were decreased by feeding supplementation with prebiotics. The quality of evidence according to the GRADE rating was both rated as low certainty. However, the feeding of prebiotics supplements on preterm infants resulted in an increased stool frequency. There was a high certainty of evidence according to the GRADE rating. Amissah et al. [20] considered that adding extra protein to human milk for preterm infants might increase hospital days. There was a very low certainty of evidence according to the GRADE rating. Amissah et al. [21] found that the carbohydrate supplementation of human milk in preterm infants could reduce the length of hospital stay. There was a very low certainty of evidence according to the GRADE rating. Moe-Byrne et al. [26] concluded that glutamine supplementation could reduce the time to reach full enteral nutrition with moderate evidence quality reported. AlFaleh et al. [27] pooled the studies that probiotics significantly shorted the hospital days and showed a significant reduction in time to reach full enteral feeds. There was both very low certainty of evidences according to the GRADE rating. Young et al. [28] reported that after four or 12 months supplementation of mult-inutrient, the bone mineral contest was increased. There was a low certainty of evidence according to the GRADE rating. And Verner et al. [29] demonstrated that taurine might help infants fat absorption form the gastrointestinal tract. There was a low certainty of evidence according to the GRADE rating.

Meanwhile, some SRs [15, 19, 23] reported that feeding supplementation applied to preterm infants was not effective on other health outcomes.

Morbidity of disease

Thirteen SRs [3, 14,15,16,17,18, 20,21,22, 24, 26, 27, 29] were assessed by the effect of feeding supplements on of disease prevention. All included SRs were deemed of high quality.

Six SRs [14, 16, 17, 22, 24, 27] concluded that feeding supplementation applied to preterm infants had an impact on disease morbidity. Pammi et al. [14] suggested that lactoferrin supplementation of enteral feeds decreased late-onset sepsis. There was a low certainty of evidence according to the GRADE rating. Pammi et al. also reported that lactoferrin supplementation on preterm infants could reduce the morbidity of fungal sepsis. There was a moderate certainty of evidence according to the GRADE rating. Chi et al. [16] showed that the use of prebiotics with preterm infants could decrease the incidence of sepsis. There was a high certainty of evidence according to the GRADE rating. Armanian et al. [17] reported that probiotic feeding reduced the incidence of hyperbilirubinaemia. There was a low certainty of evidence according to the GRADE rating. Shah et al. [22] concluded that the feeding supplementation of ariginine could reduce the morbidity of NEC. There was a moderate certainty of evidence according to the GRADE rating. Aceti et al. [24] showed that probiotics supplementation could resulted in a significantly lower incidence of LOS. There was a high certainty of evidence according to the GRADE rating. And AlFaleh et al. [27] concluded that enteral supplementation of probiotics could prevent severe NEC in preterm infants. There was a low certainty of evidence according to the GRADE rating.

However, the current available reviews [3, 15, 18, 20, 21, 26, 29] indicated that the feeding supplementation of inositol, iodine, protein, carbohydrate, Vitamin D, glutamine and taurine showed no effect on disease morbidity of preterm infants.

All-cause mortality

Eight SRs [3, 15,16,17, 22, 26, 27, 29] included data to perform the meta-analysis for the effect of feeding supplements on morbidity. All included SRs were deemed of high quality.

Three SRs [3, 16, 27] concluded that feeding supplementation applied to preterm infants have an impact on morbidity. Howlett et al. [3] revealed that there was reduction in neonatal death with inositol supplementation. There was a moderate certainty of evidence according to the GRADE rating. Chi et al. [16] showed that the use of probiotics with preterm infants decreased the mortality. There was a high certainty of evidence according to the GRADE rating. And AlFaleh et al. [27] concluded that enteral supplementation of probiotics prevented all-cause mortality in preterm infants. There was a very low certainty of evidence according to the GRADE rating.

Five SRs [15, 17, 22, 26, 29] concluded that the additional feeding supplementation of iodine, prebiotics, arginine, glutamine and taurine had no influence on all-cause mortality. Among them, although Shah et al. [22] also indicated no effect of arginine on mortality, but the death related to NEC was reported to be reduced. There was a moderate certainty of evidence according to the GRADE rating.

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