Infant-driven versus Practitioner-driven Feeding of Preterm Infants: A Systematic Review of Randomized Controlled Trials

Abstract

Background

Oral feeding should be mindful of individual ability. It is important that caregivers and parents are made aware of the infant’s behavioral signs to prevent distress. This type of feeding is based on responding to infant cues, and we call it “infant driven.” The traditional type of feeding is characterized by prescribing a predefined amount of liquid to be given at scheduled times and we call it “practitioner driven.”

Objective

To assess whether infant-driven feeding results in earlier full oral feeding compared to practitioner-driven feeding.

Methods

We included randomized controlled trials (RCTs) and searched MEDLINE and the Cochrane Library on 26 June 2024. The primary outcome was days to full oral feeding, and the effect measure was the mean difference. A meta-analysis was conducted using the inverse variance method and random effects model, and we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results

Twelve RCTs matched the inclusion criteria. Of those, five studies were included in a meta-analysis. The estimated mean difference favored infant-driven groups when compared to practitioner-driven groups: −4.93 (95% confidence interval −6.60 to −3.26, p < 0.00001, I² = 66%). The certainty of the evidence was graded as moderate.

Conclusions

The evidence base is compatible with a slight favorable effect of infant-driven feeding of preterm infants compared to practitioner-driven feeding of preterm infants. Future studies could provide more data on adverse events during feeding and add information obtained from follow-up at home.

Zusammenfassung

Hintergrund

Voraussetzung für eine erfolgreiche orale Ernährung ist die Berücksichtigung des individuellen Entwicklungsstands der Frühgeborenen. Pflegekräfte und Eltern sollten geschult sein, wie sie Verhaltenssignale des Säuglings während des Fütterns erkennen und darauf angemessen reagieren können. Diese Art der Ernährung wird in dieser Arbeit als „signalorientiertes und co-reguliertes“ Füttern von Frühgeborenen bezeichnet. Im Unterschied zeichnet sich das „herkömmliche“ Füttern dadurch aus, dass eine vorab festgelegte Flüssigkeitsmenge zu einer festgelegten Zeit verabreicht wird.

Zielsetzung

Es soll untersucht werden, ob das „signalorientierte und co-regulierte“ Füttern im Vergleich zum „herkömmlichen“ Füttern zu einer früheren vollständigen oralen Ernährung führen kann.

Methoden

Wir haben am 26. Juni 2024 in den elektronischen Datenbanken MEDLINE und Cochrane Library nach thematisch relevanten randomisierten Studien gesucht. Als primärer Endpunkt wurde die Anzahl der Tage bis zur vollständigen oralen Ernährung und als Effektmaß die mittlere Differenz gewählt. Die Metaanalyse wurde unter Verwendung der inversen Varianzmethode und des Random-Effects-Modells durchgeführt, und wir verwendeten den GRADE-Ansatz (Grading of Recommendations Assessment, Development, and Evaluation) für die Bewertung der Evidenz.

Ergebnisse

In der Studienauswahl fanden sich 12 randomisierte Studien, die den Einschlusskriterien entsprachen. Von diesen wurden 5 Studien in eine Metaanalyse einbezogen. Die geschätzte mittlere Differenz favorisierte die Gruppen mit signalorientiertem und co-reguliertem Füttern im Vergleich zu den Gruppen mit herkömmlicher Fütterung: −4,93 (95%-Konfidenzintervall −6,60 bis −3,26, p < 0,00001, I² = 66%). Die Qualität der Evidenz wurde als moderat eingestuft.

Schlussfolgerungen

Die Daten der Studienteilnehmer sind mit einem leicht vorteilhaften Effekt für die signalorientierte und co-regulierte Ernährung von Frühgeborenen im Vergleich zur herkömmlichen Ernährung von Frühgeborenen vereinbar. Zukünftige Studien könnten weitere Daten zu unerwünschten Ereignissen während der Ernährung und Informationen zur häuslichen Nachsorge ergänzen.

Keywords

preterm infant - perinatal center - neonatal intensive care - infant nutritional physiological phenomena - randomized controlled trials - meta-analysis

Schlüsselwörter

Frühgeborene - Perinatalzentrum - neonatale Intensivmedizin - Ernährungsphysiologie - randomisierte Studien - Metaanalyse

Introduction

According to the American Academy of Pediatrics, the timing of hospital discharge of the high-risk neonate includes sustained weight gain, feeding by breast or bottle without cardiorespiratory compromise, and parents and caregivers who can provide the appropriate feeding technique [1]. There are two models of oral feeding: practitioner-driven feeding and infant-driven feeding [2]. Practitioner-driven feeding means that infants are fed according to scheduled volumes and time intervals that are primarily based on weight and gestational age [3]. However, continued feeding beyond satiety might cause a stressful feeding experience and possibly an increase in the infants’ oral aversion to breast and bottle feedings [3]. Infant-driven feeding means a structured feeding method that standardizes neonatal cue-based feedings and matches the neurodevelopmental stage of the preterm infant [4]. Infants born at less than 35 weeks’ gestational age often have feeding difficulties [4] because the suck–swallow–breath pattern is not yet fully developed [5]. The successful initiation of oral feeding in preterm infants is best done in response to the infant’s developmental cues [3]. If nurses are trained to recognize the cues for readiness and hunger, then this method allows infants to orally feed the volume that they are ready for [4]. According to Ramdas 2023 [6], “The progression from nasogastric tube feedings to oral feeding is driven by the infant’s neurodevelopmental maturity. The aim of feeding advancements during the NICU stay focuses on avoiding stress related to feeding, while maintaining positive feeding experiences for the preterm infants and parents as much as possible.”

Objective

This systematic review aimed to assess whether infant-driven feeding can result in earlier full oral feeding when compared to practitioner-driven feeding.

Methods

When preparing this systematic review, we endorsed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, adhered to its principles and followed its checklist [7]. The PROSPERO registration number is CRD42024597286.

Inclusion criteria

The inclusion criteria are summarized in [Table 1].

Table 1 Inclusion criteria.

Item	Description
Study design	Randomized controlled trials with parallel assignment Not considered: Test and control intervention investigated in the same patient group such as in a crossover design
Participants	Preterm infants with a gestational age of < 37 weeks at birth
Intervention	Infant-driven oral feeding. Various labels are used to denote variants of feeding approaches that are based on responding to infant cues, although exact definitions may not be identical among them. Cue-based feeding Signal-oriented feeding Co-regulated feeding Infant-guided feeding Infant-driven feeding Response feeding Ad libitum feeding Demand feeding Semi-demand feeding Parental-guided responsive feeding
Comparator	Practitioner-driven feeding. Various labels are used to denote variants of feeding approaches that are based on prescribing volumes given at scheduled intervals, although exact definitions may not be identical among them. Practitioner-driven feeding Traditional feeding Scheduled feeding Traditional feeding Volume-based feeding Standard-care feeding Prescribed feeding Imposed regulation Force feeding Gavage feeding
Outcomes	Primary outcome Days to full oral feeding Secondary outcomes Length of hospital stay Adverse events
Publication, Types	Article publications in peer-reviewed journals Not considered: abstract publications including meeting abstracts, ongoing studies, trial registry results; secondary data such as those from systematic reviews, meta-analyses, comments, letters, narrative reviews, editorials opinions; duplicate publications. If costs or health-related quality of life were the only outcomes, then these studies were also not considered.
Languages	English, German

Design and participants

We considered randomized controlled trials (RCTs) in English or German with parallel assignment of preterm infants who showed readiness for oral feeding. We included preterm infants with a gestational age of less than 37 weeks (36 weeks and 6 days) at birth. To describe the length of gestation and age in neonates, we used the age terminology for the perinatal period published by the American Academy of Pediatrics Committee on Fetus and Newborn [8].

Interventions and publications

The test intervention was infant-driven feeding. Various labels are used to denote variants of feeding approaches that are based on responding to infant cues. The control intervention was practitioner-driven feeding. Various labels are also used to denote variants of feeding approaches that are based on prescribing volumes given at scheduled intervals. We included article publications in peer-reviewed journals and we did not consider abstract publications, secondary data, and duplicate publications. We included articles written in English and German.

Primary outcome

The primary outcome was days to full oral feeding. This outcome is important because full oral feeding is generally regarded as a prerequisite of hospital discharge and the basis for successful growth at home. During the hospital stay, experienced nurses provide gavage feeding which can assist infant growth. At home, gavage feeding can cause risks such as tube dislodgement and difficulty with tube replacement, with malposition, and risk of aspiration. The reporting of “age” might be misleading since infants were born at different gestational ages and oral feeding may have commenced at different postnatal ages. Therefore, we did not extract those data.

Secondary outcomes

Secondary outcome was length of hospital stay. We described adverse events but did not conduct a meta-analysis due to limited data. We reasoned that weight gain is not a convincing patient-centered endpoint because weight gain can be influenced by various reasons and is prone to bias, especially when observed after a short period of time.

Search strategy

We performed an unrestricted electronic literature database search in MEDLINE (PubMed, U.S. National Library of Medicine) on 22 June 2025. The MEDLINE search strategy is shown in [Table 2]. Due to automated term mapping, use of an asterisk (*) as a wild card for truncation, different spelling, or use of synonyms was not necessary. We conducted an additional electronic literature database search in The Cochrane Library (Wiley) on 22 June 2025. The Cochrane search strategy is shown in [Table 3]. MeSH terms were combined with text terms to ensure a comprehensive and up-to-date search. We searched in online trial registries on 22 June 2025 without applying limits. To search in ClinicalTrials.gov (CT.gov, https://clinicaltrials.gov/, U.S. National Library of Medicine), we used the query as follows: Condition/disease: “preterm infant” | Other terms: “premature infant” | Intervention/treatment: “feeding” | Age: “child (birth – 17)” | Study phase: “phase 2” or “phase 3” | Study type: “interventional” | Outcome measure: “full oral feeding”.

To search in the International Clinical Trials Registry Platform (ICTRP, https://trialsearch.who.int, World Health Organization), we used the queries "Cue-based feeding preterm infants" and “Response feeding preterm infants.” We searched reference lists of recent publications, Google, and we used PubMed tools including similar articles and clinical queries. We limited the search for abstracts by relying on the pre-searched results retrieved from CENTRAL which included subject-related abstracts from Embase.

Table 2 MEDLINE search strategy^(a).

Search	Query	Results
(a) MEDLINE: via PubMed using automated term mapping; no limits were used; search was customized to detect primarily randomized controlled trials (RCT); first search date 26 June 2024; second search date 22 June 2025; [edat]: Entry Date – The date the citation first entered PubMed
#1	(preterm OR premature) infant	148954
#2	low birth weight infant	56392
#3	#1 OR #2	174170
#4	(cue-based OR signal-oriented OR co-regulated OR infant-guided OR infant-driven OR response OR ad libitum OR demand OR oral OR nipple) feeding	90059
#5	random OR randomly OR randomized	1775988
#6	#3 AND #4 AND #5	614
#7	#6 AND 2024/06/26:2025/06/22 [edat]	41

Table 3 Cochrane search strategy^(a).

Search	Query	Results
(a) Cochrane Library via Wiley; Trials database; no limits were used; search was customized to detect primarily randomized controlled trials (RCT); first search date 26 June 2024 (Cochrane Reviews n = 352, Cochrane Protocols n = 28, Trials n = 767); second search date 22 June 2025 with Cochrane Library publication date from Jun 2024 to Jun 2025 (Cochrane Reviews n = 18, Cochrane Protocols n = 12, Trials n = 67, Clinical Answers n = 1)
#1	MeSH descriptor: [Infant, Premature] explode all trees	5837
#2	preterm infant*	13658
#3	premature infant*	12779
#4	MeSH descriptor: [Infant, Low Birth Weight] explode all trees	3041
#5	low birth weight infant*	7409
#6	#1 OR #2 OR #3 OR #4 OR #5	570242
#7	(cue-based OR signal-oriented OR co-regulated OR infant-guided OR infant-driven OR response OR ad libitum OR demand OR oral OR nipple)	90059
#8	Feeding	30000
#9	#7 AND #8	9926
#10	#6 AND #9	1419
#11	MeSH descriptor: [Random Allocation] explode all trees	26024
#12	MeSH descriptor: [Randomized Controlled Trial] explode all trees	37
#13	MeSH descriptor: [Randomized Controlled Trials as Topic] explode all trees	54939
#14	random*	1427222
#15	#11 OR #12 OR #13 OR #14	1427337
#16	#10 AND #15	1154
#17	with Cochrane Library publication date from Jun 2024 to Jun 2025	98

Data collection

Author #2 imported bibliographic information into Excel (Microsoft) and EndNote X9 (Clarivate), and Author #2 and Author #1 selected relevant studies in a two-step screening process. In the first step, the selection of potentially relevant references was based on title and/or abstract. In the second step, the inclusion of relevant studies was based on the full text and reasons were given for the exclusion of the remaining articles. Author #2 and Author #1 also independently extracted information from the articles. Regarding the main study characteristics of included randomized controlled trials, we extracted information on study design, country of origin, timeframe, eligible population, outcomes, trial registry number, and the numbers of assigned participants to the infant-driven arm as well as the practitioner-driven arm. We also transferred the numbers for screened, excluded, randomized, dropouts, and analyzed data.

Data analysis

Data were analyzed using Cochrane Review Manager 5 (The Cochrane Collaboration). For continuous data such as days to full oral feeding and length of hospital stay, we extracted the mean values and the corresponding standard deviations. The mean difference was the effect measure for continuous data. We assessed the clinical heterogeneity, and we estimated the percentage for the statistical heterogeneity between studies that was not due to sampling variation using the index of heterogeneity (I² statistic) [9]. An I² statistic equal to or greater than 50% was regarded as substantial heterogeneity. If the standard error (SE) was reported instead of the standard deviation (SD), then we calculated the standard deviation by multiplying the standard error with the square root of the number of participants in the respective group (SD = SE * N^1/2). If the median and the range or the interquartile range was reported, then we estimated the mean and the corresponding standard deviation using the web-based calculators https://meta-converter.com/conversions/mean-sd-range and https://meta-converter.com/conversions/mean-sd-iqr, which are based on the formulas published by Wan 2014 [10]. For dichotomous data such as adverse events, we planned to extract the number of participants who experienced the events and the total number of participants in the respective group. Due to limited data, we did not conduct a meta-analysis concerning adverse events but used instead the data in a descriptive analysis.

Assessment of risk of bias

Two authors independently appraised the risk of bias in the included studies. Differences in opinions were resolved by discussion and the assistance of a third author was not necessary. We used the items listed in Cochrane’s tool for assessing risk of bias [11]. We assessed selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.

Grading the certainty of evidence

We adopted the GRADE approach to define the certainty of a body of identified evidence as described in the Cochrane Handbook for Systematic Reviews of Interventions [12]. We established the initial level of certainty based on study design, considered lowering the level of certainty based on risk of bias, inconsistency, indirectness, imprecision, and publication bias, and we rated the certainty in an estimate of effect across those considerations as high, moderate, low, or very low. For the primary beneficial outcome and the primary adverse outcome, two review authors independently assessed the quality of the evidence using the GRADE considerations.

Results

Search results

[Fig. 1] shows the PRISMA flow diagram. We retrieved 1490 references from databases and registers. In the first step of screening, we considered 1437 references as not relevant to this review. In the second step, we assessed the full-text publications of the remaining 53 references. We identified 10 relevant studies (12 references), and the exclusion criteria for the other 41 references are listed in [Table 4]. We identified two additional relevant studies after searching reference lists of recent systematic reviews. [Table 5] lists the total number of 12 studies (14 references) included in this systematic review [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]. For all studies but one [13], the table shows the primary reference of each included study. [Table 6] shows six recent systematic reviews and the RCTs which they included [25] [26] [27] [28] [29] [30]. Two excluded references report on ongoing RCTs that should be considered in future updates [31] [32].

Fig. 1 PRISMA 2020 flow diagram. Reference: Page MJ et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. DOI: 10.1136/bmj.n71.

Table 4 Excluded references (n = 41).

No	Reference	Not of interest
Abbreviation: NCT = ClinicalTrials.gov identifier (National Clinical Trial number). Duplicates: n = 12; not population of interest: n = 2; not intervention of interest: n = 9; not study design: n = 4; meeting abstract only: n = 1; crossover randomized controlled trial: n = 1; systematic review: n = 8
1	Arianas EA, Rankin KM, Norr KF, White-Traut RC. Maternal weight status and responsiveness to preterm infant behavioral cues during feeding. BMC Pregnancy Childbirth 2017; 17(1): 113	Intervention
2	Arianas EA, Rankin KM, Norr KF, White-Traut RC. Maternal weight status and responsiveness to preterm infant behavioral cues during feeding. BMC Pregnancy Childbirth 2017; 17(1): 113	Duplicate
3	Avila-Galindo SL, Thompson-Chagoyan OC. Comparison of an individualized feeding technique on hospital stay and body composition in preterm infants. Meeting abstracts of the Ibero-American Nutrition Foundation (FINUT) in Mexico City, Mexico from 09 to 11 October 2022. Abstract P067, page 153. Ann Nutr Metab 2023; 79(1): 49–218	Meeting abstract only
4	Celen R, Tas-Arslan F, Soylu H. Effect of SINC feeding protocol on weight gain, transition to oral feeding, and the length of hospitalization in preterm infants: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2021; 45(3): 567–577	Duplicate
5	Chang SR, Chen KH. Demand feeding for healthy premature newborns: a randomized crossover study. J Formos Med Assoc 2004; 103(2): 112–117	Crossover RCT
6	Chang SR, Chen KH. Demand feeding for healthy premature newborns: a randomized crossover study. J Formos Med Assoc 2004; 103(2): 112–117	Duplicate
7	Collinge JM, Bradley K, Perks C, Rezny A, Topping P. Demand vs. scheduled feedings for premature infants. JOGN Nurs 1982; 11(6): 362–367	Duplicate
8	Crowe L, Chang A, Wallace K. Instruments for assessing readiness to commence suck feeds in preterm infants: effects on time to establish full oral feeding and duration of hospitalisation. Cochrane Database Syst Rev 2016; 2016(8): CD005586	Intervention
9	CTRI/2025/01/079609. Infant driven cue based feeding vs physician driven scheduled paladai feeding in preterm neonates born less than or equal to 32 weeks. [https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2025/01/079609]	Registry
10	Dalgleish SR, Kostecky LL, Blachly N. Eating in “SINC”: Safe individualized nipple-feeding competence, a quality improvement project to explore infant-driven oral feeding for very premature infants requiring noninvasive respiratory support. Neonatal Netw 2016; 35(4): 217–227	Study design
11	Edmond K, Strobel N. Evidence for global health care interventions for preterm or low birth weight infants: an overview of systematic reviews. Pediatrics 2022; 150 (Suppl. 1)	Intervention
12	Fry TJ, Marfurt S, Wengier S. Systematic review of quality improvement initiatives related to cue-based feeding in preterm infants. Nurs Womens Health 2018; 22(5): 401–410	Systematic review
13	Griffith T, Rankin K, White-Traut R. The relationship between behavioral states and oral feeding efficiency in preterm infants. Adv Neonatal Care 2017; 17(1): E12–E19	Intervention
14	Griffith T, Rankin K, White-Traut R. The relationship between behavioral states and oral feeding efficiency in preterm infants. Adv Neonatal Care 2017; 17(1): E12–E19	Duplicate
15	Hails KA, Whipps MDM, Gross RS, Bogen DL, Morris PA, Mendelsohn AL et al. Breastfeeding and responsive parenting as predictors of infant weight change in the first year. J Pediatr Psychol 2021; 46(7): 768–778	Population
16	Hails KA, Whipps MDM, Gross RS, Bogen DL, Morris PA, Mendelsohn AL et al. Breastfeeding and responsive parenting as predictors of infant weight change in the first year. J Pediatr Psychol 2021; 46(7): 768–778	Duplicate
17	Horodynski MA, Olson B, Baker S, Brophy-Herb H, Auld G, Van Egeren L et al. Healthy babies through infant-centered feeding protocol: an intervention targeting early childhood obesity in vulnerable populations. BMC Public Health 2011; 11: 868	Population
18	Lau C, Schanler RJ. Oral feeding in premature infants: advantage of a self-paced milk flow. Acta Paediatr 2000; 89(4): 453–459	Intervention
19	Lucas A, Sherman J, Fewtrell M. Postdischarge nutrition in preterm infants. Neoreviews 2022; 23(8): e541–e557	Intervention
20	McCain GC, Gartside PS, Greenberg JM, Lott JW. A feeding protocol for healthy preterm infants that shortens time to oral feeding. J Pediatr 2001; 139(3): 374–379	Duplicate
21	McCain GC, Del Moral T, Duncan RC, Fontaine JL, Pino LD. Transition from gavage to nipple feeding for preterm infants with bronchopulmonary dysplasia. Nurs Res 2012; 61(6): 380–387	Duplicate
22	McCormick FM, Tosh K, McGuire W. Ad libitum or demand/semi-demand feeding versus scheduled interval feeding for preterm infants. Cochrane Database Syst Rev 2010(2): CD005255	Systematic review
23	McFadden A, Fitzpatrick B, Shinwell S, Tosh K, Donnan P, Wallace LM et al. Cue-based versus scheduled feeding for preterm infants transitioning from tube to oral feeding: the Cubs mixed-methods feasibility study. Health Technol Assess 2021; 25(74): 1–146	Systematic review
24	Morag I, Hendel Y, Karol D, Geva R, Tzipi S. Transition from nasogastric tube to oral feeding: the role of parental guided responsive feeding. Front Pediatr 2019; 7: 190	Duplicate
25	NCT01989871. Adjusted individual oral feeding for improving short- and long-term outcomes of preterm infants. [https://clinicaltrials.gov/ct2/show/NCT01989871]	Study design
26	NCT04946045. Feeding Readiness and Oral Feeding Success in Preterm Infants. [https://clinicaltrials.gov/ct2/show/NCT04946045]	Intervention
27	NCT06569186. Cue-based vs. clinician-driven feeding in very low birthweight infants [https://clinicaltrials.gov/study/NCT06569186]	Registry
28	NCT06569186. Cue-based vs. clinician-driven feeding in very low birthweight infants [https://clinicaltrials.gov/study/NCT06569186]	Duplicate
29	Pickler RH, Reyna BA, Wetzel PA, Lewis M. Effect of four approaches to oral feeding progression on clinical outcomes in preterm infants. Nurs Res Pract 2015; 2015: 716828	Intervention
30	Pridham K, Kosorok MR, Greer F, Carey P, Kayata S, Sondel S. The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain. Nurs Res 1999; 48: 86–93	Duplicate
31	Pridham KF, Kosorok MR, Greer F, Kayata S, Bhattacharya A, Grunwald P. Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries. J Adv Nurs 2001 Sep; 35(5): 751–759	Duplicate
32	Ramdas D, Drury N, Jordan C, Panda S, Singh AP. Effects of infant driven feeding program on provision of breast milk in very low birth weight infants. Breastfeed Med 2023; 18(4): 272–278	Study design
33	Samane S, Yadollah ZP, Marzieh H, Karimollah HT, Reza ZM, Afsaneh A et al. Cue-based feeding and short-term health outcomes of premature infants in newborn intensive care units: a non-randomized trial. BMC Pediatr 2022; 22(1): 23	Study design
34	Samane S, Yadollah ZP, Marzieh H, Karimollah HT, Reza ZM, Afsaneh A et al. Cue-based feeding and short-term health outcomes of premature infants in newborn intensive care units: a non-randomized trial. BMC Pediatr 2022; 22(1): 23	Duplicate
35	Settle M, Francis K. Does the infant-driven feeding method positively impact preterm infant feeding outcomes? Adv Neonatal Care 2019; 19(1): 51–55	Systematic review
36	Talej M, Smith ER, Lauria ME, Chitale R, Ferguson K, He S. Responsive feeding for preterm or low birth weight infants: a systematic review and meta-analysis. Pediatrics 2022; 150 (Suppl 1)	Systematic review
37	Tosh K, McGuire W. Ad libitum or demand/semi-demand feeding versus scheduled interval feeding for preterm infants. Cochrane Database Syst Rev 2006(3): CD005255	Systematic review
38	Watson J, McGuire W. Responsive versus scheduled feeding for preterm infants. Cochrane Database Syst Rev 2015(10): CD005255	Systematic review
39	Watson J, McGuire W. Responsive versus scheduled feeding for preterm infants. Cochrane Database Syst Rev 2016; 2016(8): CD005255	Systematic review
40	Yucel A, Kucukoglu S, Soylu H. The effect of breast milk odor on feeding cues, transition time to oral feeding, and abdominal perfusion in premature newborns: a randomised controlled trial. Biol Res Nurs 2024; 26(1): 160–175	Intervention
41	Zhang X, Liu H, Yang Y, Mao C. Effect of cue-based feeding on the feeding outcomes of preterm infants: a systematic review and meta-analysis. J Adv Nurs 2025; 81(5): 2793–2809	Systematic review

Table 5 Included studies (n = 12), associated references (n = 14).

Study ID	References
Abbreviation: NCT = ClinicalTrials.gov identifier (National Clinical Trial number)
Celen 2021	Celen R, Tas-Arslan F, Soylu H. Effect of SINC feeding protocol on weight gain, transition to oral feeding, and the length of hospitalization in preterm infants: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2021; 45(3): 567–577 NCT03371927: Celen R, Tas-Arslan F, Soylu H. Effect of SINC feeding protocol on weight gain, transition to oral feeding, and the length of hospitalization [https://clinicaltrials.gov/ct2/show/NCT03371927]. 2019 WCPM Meeting: Celen R, Tas-Arslan F, Soylu H. O1278 – Effect of safe individualized nipple feeding competence (SINC) feeding protocol on weight gain transition to oral feeding and the length of hospitalization in premature infants randomized controlled study. Oral presentation at the 14th World Congress of Perinatal Medicine (WCPM), Istanbul, Turkey, 2019 [https://www.degruyterbrill.com/document/doi/10.1515/jpm-2019-2501/html].
Collinge 1982	Collinge JM, Bradley K, Perks C, Rezny A, Topping P. Demand vs. scheduled feedings for premature infants. JOGN Nurs 1982; 11(6): 362–367
Kamran 2020	Kamran F, Khatoonabadi AR, Aghajanzadeh M, Ebadi A, Faryadras Y, Sagheb S. Effectiveness of cue-based feeding versus scheduled feeding in preterm infants using comprehensive feeding assessment scales: a randomized clinical trial. Iran J Pediatr 2020; 30(6): e107475
McCain 2001	McCain GC, Gartside PS, Greenberg JM, Lott JW. A feeding protocol for healthy preterm infants that shortens time to oral feeding. J Pediatr 2001; 139(3): 374–379
McCain 2012	McCain GC, Del Moral T, Duncan RC, Fontaine JL, Pino LD. Transition from gavage to nipple feeding for preterm infants with bronchopulmonary dysplasia. Nurs Res 2012; 61(6): 380–387
Morag 2019	Morag I, Hendel Y, Karol D, Geva R, Tzipi S. Transition from nasogastric tube to oral feeding: the role of parental guided responsive feeding. Front Pediatr 2019; 7: 190
Pridham 1999	Pridham K, Kosorok MR, Greer F, Carey P, Kayata S, Sondel S. The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain. Nurs Res 1999; 48: 86–93
Pridham 2001	Pridham KF, Kosorok MR, Greer F, Kayata S, Bhattacharya A, Grunwald P. Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries. J Adv Nurs 2001 Sep; 35(5): 751–759
Puckett 2008	Puckett B, Grover VK, Holt T, Sankaran K. Cue-based feeding for preterm infants: a prospective trial. Am J Perinatol 2008; 25(10): 623–628
Saunders 1991	Saunders RB, Friedman CB, Stramoski PR. Feeding preterm infants. Schedule or demand? J Obstet Gynecol Neonatal Nurs 1991; 20(3): 212–218
Solanki 2022	Solanki J, Bookseller MH. Efficacy of cue-based versus scheduled feeding in low-birth-weight preterm neonates. Perinatology 2022–2023; 23(3–4): 134–138
Waber 1998	Waber B, Hubler EG, Padden ML. A comparison of outcomes in demand versus schedule formula-fed premature infants. Nutr Clin Pract 1998; 13(3): 132–135

Table 6 RCTs included in recent systematic reviews.

	This review	Reason for exclusion	Zhang 2025	Talej 2022	McFadden 2021	Settle 2019	Fry 2018	Watson 2016
Abbreviations: – = not reported/not included; HTA = health technology assessment; SR/MA = systematic review/meta-analysis (a) The five most common outcomes according to McFadden 2021
Type of publication	SR/MA		SR/MA	SR/MA	HTA	SR/MA	SR/MA	SR/MA
Search date			22 Nov 2023	31 Mar 2021	Aug 2018	–	Nov 2017	17 Feb 2016
Five most common outcomes(a)
Time to full oral feeding	Yes		Yes	–	Yes	Yes	Yes	Yes
Length of hospital stay	Yes		–	Yes	Yes	Yes	Yes	Yes
Weight gain	–		–	Yes	Yes	–	Yes	Yes
Respiratory complications	–		–	–	Yes	–	–	–
Daily volume intake	–		–	–	Yes	–	–	–
Randomized controlled trials
Celen 2021	Yes		–	–	–	–	–	–
Collinge 1982	Yes		–	Yes	Yes	–	–	Yes
Kamran 2020	Yes		–	Yes	–	–	–	–
Kansas 2004	–	Abstract	–	Yes	Yes	–	–	Yes
McCain 2001	Yes		–	Yes	Yes	–	–	Yes
McCain 2012	Yes		–	Yes	Yes	–	–	Yes
Morag 2019	Yes		–	Yes	–	–	–	–
Pridham 1999	Yes		–	Yes	Yes	–	–	Yes
Pridham 2001	Yes		–	Yes	Yes	–	–	Yes
Puckett 2008	Yes		Yes	Yes	Yes	Yes	–	Yes
Saunders 1991	Yes		–	Yes	Yes	–	–	Yes
Solanki 2023	Yes		–	–	–	–	–	–
Waber 1998	Yes		–	Yes	Yes	–	–	Yes
Total	12	1	1	11	9	1	0	9

Baseline data

[Table 7] provides an overview of the main study characteristics. The design details of all 12 included studies can be described as follows: primary purpose: treatment; allocation: randomized; interventional model: parallel assignment; interventional model description: intervention and control groups; masking: none (open label) [33]. Six trials originated in the United States, two in Canada, and the remaining four in Asia. The recruitment period ranged from 1980 to 2020. Eleven studies used gestational age to define eligibility, which ranged from less than 34 to less than 37 weeks. Five studies requested a minimum birth weight ranging from 1200 g to 1800 g. One study limited the analysis to participants with bronchopulmonary dysplasia. The number of analyzed participants in the infant-driven arm ranged from 15 to 132. The number of analyzed participants in the practitioner-driven arm ranged from 14 to 122. Six studies reported the outcome “age of or time to full oral feeding”, whereas the rest of six studies reported the outcome weight gain. Three studies were registered. Most studies reported various types of liquid ingestion such as the use of feeding bottle, injector, or mother’s breast. If breast milk was not available, preterm infant formula was provided.

Table 7 Study characteristics of included RCTs.

Study ID	Country	NICU	Recruitment period	GA	Screened/excluded/randomized	Dropouts/analyzed	Infantdriven	Practitioner driven	Registry
Abbreviations: – = not reported; < = smaller than; GA = gestational age at birth in weeks; ID = identifier; IRCT = Iranian Registry of Clinical Trials; NCT = ClinicalTrials.gov identifier; NICU = (level of) neonatal intensive care unit; RCTs = randomized controlled trials; SHEBA = Sheba Medical Center clinical trials identifier (a) Collinge 1982: eligible population: birthweight 1.8 to 2.5 kg (b) Morag 2019: the study was also registered with SHEBA-12–9574-IM-CTIL
Celen 2021	Turkey	III	Feb 2018–Mar 2019	28 to < 34	176/96/80	4/76	37	39	NCT03371927
Collinge 1982	Canada	–	Apr 1980–May 1981	n. r.(a)	46/10/36	–/36	18	18	–
Kamran 2020	Iran	–	Dec 2017–Feb 2018	< 34	– /n –/37	–/37	18	19	IRCT20180611040062N1
McCain 2001	United States	–	–	< 34	89/8/81	–/81	40	41	–
McCain 2012	United States	–	Mar 2006–Mar 2009	< 34	150/54/96	10/86	44	42	–
Morag 2019	Israel	–	Nov 2013–Nov 2016	< 32	208/133/75	8/67	32	35	NCT01989871(b)
Pridham 1999	United States	III	–	< 35	178/100/78	–/78	45	33	–
Pridham 2001	United States	III	–	< 35	338/238/100	–/100	58	42	–
Puckett 2008	Canada	III	2001–2003	32 to < 37	181/102/79	–/79	39	40	–
Saunders 1991	United States	III	–	< 37	–/–/32	3/29	15	14	–
Solanki 2023	India	III	Mar 2020–Nov 2020	32 to < 37	–/–/305	51/254	132	122	–
Waber 1998	United States	III	–	< 34	–/–/13	3/10	5	5	–

Outcomes

[Table 8] provides an overview of the outcome data reported in the 12 RCTs. For the primary outcome, [Fig. 2] shows that the pooled estimate of days to full oral feeding favors infant-driven feeding compared to practitioner-driven feeding in five RCTs [13] [15] [16] [17] [18]: mean difference −4.93 (95% confidence interval −6.60 to −3.26, p < 0.00001, I² = 66%). The corresponding primary data of the RCTs are shown in [Table 8].

Table 8 Outcomes of included RCTs.

Study ID	Participants	Days to full oral feeding	Length of hospital stay
	Infant-driven vs practitioner- driven	Days, mean (SD)	Days, mean (SD)
Abbreviations: – = not reported; ID = identifier; RCTs = randomized controlled trials; SD = standard deviation (a) The standard deviation (SD) was estimated from the standard error of the mean (SE) using the formula SD = SE * N1/2; N = number of participants in a group. (b) The mean and standard deviation (SD) was estimated from the median and interquartile range (IQR) using the web application
Celen 2021	37 vs 39	34.84 (22.92) vs 36. 49 (26.02)	38.27 (23.1) vs 41.64 (28.26)
Collinge 1982	18 vs 18	8.9 (–) vs 2.7 (–)	–
Kamran 2020	18 vs 19	3.55 (1.24) vs 6.68 (2.00)	15.55 (5.38) vs 27.10 (7.90)
McCain 2001	40 vs 41	5 (4.2) vs 10 (3.1)	–
McCain 2012(a)	44 vs 42	5.9 (4.64) vs 12.3 (5.18)	106.9 (27.6) vs 115.9 (39.4)
Morag 2019(b)	32 vs 35	2.33 (3.88) vs 9 (8.5)	–
Pridham 1999	45 vs 33	–	–
Pridham 2001	58 vs 42	–	–
Puckett 2008	39 vs 40	–	10.0 (3.4) vs 14.5 (4.3)
Saunders 1991	15 vs 14	–	7.2 vs 8.4
Solanki 2023(b)	132 vs 122	–	5.67 (3) vs 8.67 (6)
Waber 1998	– vs –	–	31 vs 33

Fig. 2 Forest plot of infant-driven feeding vs practitioner-driven feeding, primary outcome: mean difference of days to full oral feeding. 95% CI: 95% confidence interval; I²: index of heterogeneity (the smaller the value, the lower the heterogeneity); Infant: infant-driven feeding; IV: inverse variance (statistical method); P: probability; Practitioner: practitioner-driven feeding; Random: random effects (analysis model); Mean Difference: mean difference (effect measure)

For the secondary outcome length of hospital stay, [Fig. 3] shows that the pooled estimate favors infant-driven feeding compared to practitioner-driven feeding in five other RCTs [13] [15] [17] [21] [23]: Mean difference −5.47 (95% confidence interval −8.27 to −2.67, p = 0.0001, I²= 74%).

Fig. 3 Forest plot of infant-driven feeding vs practitioner-driven feeding, secondary outcome: mean difference of days of hospitalization. 95% CI = 95% confidence interval; I² = index of heterogeneity (the smaller the value, the lower the heterogeneity); Infant = infant-driven feeding; IV = inverse variance (statistical method); Mean Difference = mean difference (effect measure); P = probability; Practitioner = practitioner-driven feeding; Random = random effects (analysis model).

For the secondary outcome adverse events, a meta-analysis was not meaningful due to limited reporting. Morag 2019 [18] reported the number of apnea/bradycardia events at 34 weeks as a median of 3.5 (interquartile range 1–13.5) for the infant-driven group and a median of 9 (interquartile range 2–18) for the practitioner-driven group. Puckett 2008 [21] reported the number of desaturations and/or apneas and/or bradycardia as a mean of 3.5 (SD 3.3) for the infant-driven group and a mean of 12.8 (SD 14.4) for the practitioner-driven group. Solanki 2022 [23] reported a feed intolerance of about 3.5% (5 out of 140) in both groups. The most common complications of feed intolerance were abdominal distension, vomiting, and high aspirate.

Risk of bias assessment

[Table 9], [Table 10], and [Table 11] provide an overview of the results of the risk of bias assessment of the included RCTs. The risk of bias summary and graph are shown in [Fig. 4], and results of individual studies included in meta-analyses are also shown together with the corresponding forest plots ([Fig. 2] and [Fig. 3]). “Random sequence generation (selection bias)” was mostly adequately described but only one study referred to “Allocation concealment (selection bias).” “Blinding of participants and personnel (performance bias)” is a difficult task, and we considered the risk of bias to be unclear if this type of blinding was not achieved. It is noteworthy that two studies did report some kind of blinding of parents or nursing personnel. Two of the 12 studies reported “Blinding of outcome assessment (detection bias)”, which is an important issue to reduce the risk of bias. We did not find clues of “Incomplete outcome data (attrition bias)” in most of the studies. We modified the criteria for “Selective reporting (reporting bias)” and found quite limited reporting quality in eight studies. The item “Other bias” was limited to the question whether there were signs of funding from industry. This was seemingly not the case since all 12 studies were funded by universities or equivalent institutions.

Fig. 4 Risk of bias summary and risk of bias graph for all 12 included RCTs.

Grading the certainty of evidence

For the primary outcome days to full oral feeding, we established an initial level of high certainty due to the randomized study design. There was substantial heterogeneity, and we downgraded by one level. There was mostly a low risk of selection bias, attrition bias, and other bias, and we did not downgrade another level. There was no inconsistency of results, and there was no indirectness of evidence. The studies included an appropriate number of participants and, apart from one study, reported narrow confidence intervals. Thus, there was no imprecision of results. There are four positive studies and one study showing no effect. There is no indication that other studies were published showing harm or no effect. The studies reported a specific intervention on a and specific disease, and there was no for-profit interest in the intervention. Thus, there was no clear indication of a publication bias. The final level of certainty rating was: Moderate ⊕⊕⊕○.

Table 9 Risk of bias assessment results.

Item	Celen 2021	Collinge 1982	Kamran 2020	McCain 2001
Random sequence generation (selection bias)	Random numbers (https://www.random.org) prepared by a statistician who was not involved in the trial, thus LOW.	The infant was randomly assigned but details were not reported, thus UNCLEAR.	Block randomization method, thus LOW.	Minimization method, thus LOW.
Allocation concealment (selection bias)	The next envelope in the sequence was opened to determine group assignment, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Blinding of participants and personnel (performance bias)	Parents were blinded (though nurses and researchers were not), thus LOW.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.
Blinding of outcome assessment (detection bias)	Outcome assessment was reportedly blinded, thus LOW.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Incomplete outcome data (attrition bias)	Four discontinued the intervention, two in each group. Attrition rates were low and comparable between groups, thus LOW.	No apparent attrition reported, thus LOW.	No apparent attrition reported, thus LOW.	Attrition rates were low and comparable between groups, thus LOW.
Selective reporting (reporting bias)	Patient flow and primary/secondary patient-centered outcomes were reported, characteristics were balanced, and intention-to-treat analysis was applied, thus LOW.	No primary/secondary outcomes, age was different between groups, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.
Other bias	The trial was registered in ClinicalTrials.gov (identifier: NCT03371927). Sponsor was Selcuk University, thus LOW.	Sponsor was the McGill University Montreal Children’s Hospital Research Institute, thus LOW.	Sponsor was the Tehran University of Medical Sciences, thus LOW.	Sponsor was the University of Cincinnati, Ohio, thus LOW.

Table 10 Risk of bias assessment results.

Item	McCain 2012	Morag 2019	Pridham 1999	Pridham 2001
Random sequence generation (selection bias)	Minimization method, thus LOW.	Randomization was accomplished by the parents taking a sealed opaque envelope from a box, thus LOW.	A computer program was used to maintain randomness of assignment, thus LOW.	A computerized ‘biased coin’ randomization strategy was used, thus LOW.
Allocation concealment (selection bias)	Not reported, thus UNCLEAR.	Randomization was accomplished by the parents taking a sealed opaque envelope from a box, thus LOW.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Blinding of participants and personnel (performance bias)	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	Nursing personnel were blinded, thus LOW.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.
Blinding of outcome assessment (detection bias)	Not reported, thus UNCLEAR.	Outcome assessment was reportedly blinded, thus LOW.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Incomplete outcome data (attrition bias)	Attrition rates were low and comparable between groups, thus LOW.	Attrition rates were low and comparable between groups, thus LOW.	Attrition rates were low and comparable between groups, thus LOW.	No apparent attrition reported, thus LOW.
Selective reporting (reporting bias)	No primary/secondary outcomes, no intention-to-treat analysis but a detailed patient flow was reported, thus UNCLEAR.	Patient flow and primary/secondary patient-centered outcomes were reported, characteristics were balanced, and intention-to-treat analysis was applied, thus LOW.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.
Other bias	Sponsor was the University of Miami, Florida, thus LOW.	Sponsor was the Chaim Sheba Medical Center in Israel, thus LOW.	Sponsor was the University of Wisconsin-Madison, thus LOW.	Sponsor was the University of Wisconsin-Madison, thus LOW.

Table 11 Risk of bias assessment results.

Item	Puckett 2008	Saunders 1991	Solanki 2023	Waber 1998
Random sequence generation (selection bias)	Simple randomization, no details reported, thus UNCLEAR.	Used a table of random numbers, thus LOW.	“Randomized, observational study”, no details reported, thus UNCLEAR.	Accomplished by coin toss, thus LOW.
Allocation concealment (selection bias)	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Blinding of participants and personnel (performance bias)	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.	No blinding; we believe that this issue might have influenced the results but to a minor extent, thus UNCLEAR.
Blinding of outcome assessment (detection bias)	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.	Not reported, thus UNCLEAR.
Incomplete outcome data (attrition bias)	No apparent attrition reported, thus LOW.	Attrition rates were low and comparable between groups, thus LOW.	No apparent attrition reported, thus LOW.	Of the original 13 infants successfully enrolled in the study, three were withdrawn, thus UNCLEAR.
Selective reporting (reporting bias)	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.	No intention-to-treat analysis and no patient flow but primary/secondary outcomes were reported, thus UNCLEAR.	No primary/secondary outcomes, no intention-to-treat analysis, and no patient flow was reported, thus HIGH.
Other bias	Sponsor was the Royal University Hospital, Saskatoon, thus LOW.	Sponsor was the University of North Carolina, Greensboro, thus LOW.	Sponsor was the Sayajirao General Hospital and Medical College, Baroda, thus LOW.	Sponsor was the Children’s Regional Hospital, Camden, thus LOW.

Discussion

Summary of main results

Findings from five RCTs [13] [15] [16] [17] [18] suggest that infant-driven feeding of preterm infants could result in fewer days to full oral feeding than practitioner-driven feeding. Findings from five other RCTs [13] [15] [17] [21] [23] suggest that infant-driven feeding of preterm infants could result in shorter length of hospital stay.

Overall completeness and applicability of evidence

With respect to the primary outcome days to full oral feeding, the relevant five studies were published between 2001 and 2021 [13] [15] [16] [17] [18], and we presume that the principal treatment procedures did not deviate considerably from current practice. The studies were conducted by academic institutions, and a financial conflict of interest was not obvious. It is noteworthy that the risk of bias assessment of two of those five studies [13] [18] resulted in a low risk for six out of seven items. Information required by the Consolidated Standards of Reporting Trials (CONSORT) statement [34] was provided by three studies. We included 12 studies, but seven studies did not report the primary outcome days to full oral feeding or did not report sufficient data for inclusion in a meta-analysis. This might narrow the applicability of evidence.

Subgroups and heterogeneity

We assumed significant clinical heterogeneity since gestational age at birth varied across studies. The eligible gestational age at birth ranged from less than 32 weeks to less than 37 weeks among the studies. One study limited the investigation to participants with bronchopulmonary dysplasia [17]. An identical infant-driven feeding plan could have different effects depending on the type of participants. Infant-driven feeding as well as practitioner-driven feeding of preterm infants are umbrella terms and may be applied to various protocols and procedures. It is obvious that the test treatment and likewise the control treatment differed among the five included studies. We did not find a cause for subgroup analysis. The statistical heterogeneity for the pooled estimate of the primary outcome days to full oral feeding was substantial (I² = 66%) [13] [15] [16] [17] [18].

Limitations of the evidence contained in this paper

We included 12 trials in the systematic review but only five trials provided the required data for inclusion in the meta-analysis on the primary outcome days to full oral feeding. The recruitment period covered the years from 1980 through 2020. Infant-driven feeding is still relatively new in the neonatal intensive care unit. Neonatal intensive care unit staff probably did not have access to standardized training on infant feeding in the early 1980s. Infant-driven feeding and practitioner-driven feeding are vague and not uniformly defined terms and should be understood more as a generic term for an approach than as a strict therapeutic regime. Infant-driven feeding is not only changing the type of feeding but also the entire approach to handling the preterm infant. The same nursing staff possibly carried out both types of care, possibly causing mixed effects. The risk of bias appears lower in more recent studies than in earlier studies. No financial influence could be detected in any study thanks to funding from public bodies. Gestational age at the start of the study, length of the previous hospital stay, and comorbidity differ between studies, suggesting significant clinical heterogeneity. There is no uniform standard scheme for either feeding type and it appeared that each study described a distinctive procedure. Adverse events were reported in three studies. Generally, adverse events are important for balancing benefit and harm of an intervention. We identified the reporting of adverse events in three of the 12 included trials. The results were in favor of the infant-driven groups. The data were limited, and a meaningful comparison was not warranted.

Potential bias of the review process

The present review is based on a near comprehensive search, and we provide detailed study characteristics and interpretations. Many included studies did not report seminal data on the primary outcome, and we do not know whether the outcome in those studies would converge with or diverge from our results. Overall, we did not consider that there was a high risk of bias for any study. Blinding of participants and personnel (performance bias) and blinding of outcome assessment (detection bias) might be difficult relating to the feeding of preterm infants. We chose to evaluate the risk as unclear with regards to whether blinding was not reported or not applied. In principle, the risk of bias assessment is subjective. We included studies written in English or German which did not have a notable impact.

Context

[Table 9], [Table 10], and [Table 11] provide an overview of six recent systematic reviews. We listed all presumed randomized studies included in those reviews, and we explained the reasons when studies were not included in this work. The search dates ranged from February 2016 to March 2021. The Cochrane Review by Watson 2016 [30] based its conclusions on meta-analyses of randomized data and suggested that infant-driven feeding reduced the days to full oral feeding and reported indifferent results about the length of hospital stay. The Health Technology Assessment by McFadden 2021 [27] was an update of the Cochrane Review by Watson 2016 [30]. The authors found one additional trial which did not change the conclusions. It is noteworthy that McFadden 2021 [27] listed the five most common outcome measures, which were (1) length of time to full oral feeding, (2) total length of stay/length in the neonatal unit, (3) daily weight gain, (4) respiratory complications or oxygen therapy requirements, and (5) daily volume intake. The systematic review by Talej 2022 [26] based its conclusions on meta-analyses of randomized data and suggested infant-driven feeding slightly decreased the length of hospital stay. The outcome days to full oral feeding was not evaluated. We did not regard the reviews by Zhang 2025 [25], Settle 2019 [28], and Fry 2018 [29] as meaningful systematic reviews. Zhang 2025 [25] included only one RCT published in a peer-reviewed journal. The references to five other studies could not be traced, not even with Google. Settle 2019 [28] also included the same single RCT. Fry 2018 [29] did not include any RCT. Overall, the numerical tendencies with respect to the days to full oral feeding and the length of hospital stay are in line with the results of the meta-analyses by Watson 2016 [30] and Talej 2022 [26].

Outlook

The available studies did not report on adverse events during feeding. The continuity of feeding after discharge from hospital and the wellbeing of the child at home is important. The final time-point for measuring the outcome should not stop at discharge from hospital. Follow-up of the feeding, required readmissions, return to gavage, and adverse events during feeding after discharge are also of prime interest. The description and analysis of the provided types of milk and ingestion could also be of interest. We believe that these points should be elaborated in future studies. It was difficult to understand and extract the information reported in the studies. We believe that the reporting quality should be improved in future studies by complying with the CONSORT statement [34].

Conclusions

The evidence base is compatible with a slight favorable effect of infant-driven feeding of preterm infants compared to practitioner-driven feeding of preterm. Future studies could provide more data on adverse events during feeding and add information on the follow-up at home.

Statements: Data availability: none; Ethics approval: not applicable; Patient consent: not applicable; Permission to reproduce material from other sources: not applicable.

Contributorsʼ Statement

FP created the design and critically revised the work; KBA developed the search strategy, performed the literature search and data analysis, and drafted the work.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Publication History

Received: 21 August 2025

Accepted after revision: 03 January 2026

Article published online:
06 February 2026