Succión no nutritiva para aumentar la estabilidad fisiológica y la nutrición en bebés prematuros
Resumen
Antecedentes
La succión no nutritiva (SNN) se utiliza durante la alimentación por sonda y en la transición de la alimentación por sonda a la alimentación por pecho/biberón en los bebés prematuros para mejorar el desarrollo de la conducta de succión y la digestión de la alimentación enteral.
Objetivos
Evaluar los efectos de la succión no nutritiva en la estabilidad fisiológica y la nutrición en bebés prematuros.
Métodos de búsqueda
Se utilizó la estrategia de búsqueda estándar del Grupo de Revisión Cochrane de Neonatología (Cochrane Neonatal Review Group) para buscar en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL; 2016, número 1); MEDLINE vía PubMed (1966 hasta el 25 febrero 2016); Embase (1980 hasta 25 febrero 2016); y en CINAHL (1982 hasta el 25 febrero 2016). También se buscaron ensayos controlados aleatorios en las bases de datos de ensayos clínicos, actas de congresos y en las listas de referencias de los artículos recuperados.
Criterios de selección
Ensayos controlados aleatorios y cuasialeatorios que compararon la succión no nutritiva versus la no provisión de succión no nutritiva en lactantes prematuros. Se excluyeron los ensayos cruzados (crossover).
Obtención y análisis de los datos
Dos autores de la revisión evaluaron la elegibilidad de los ensayos y el riesgo de sesgo y realizaron la extracción de datos de forma independiente. Se analizaron los efectos del tratamiento en los ensayos individuales y se informaron las diferencias de medias (DM) para los datos continuos, con intervalos de confianza (IC) del 95%. Para los metanálisis se utilizó un modelo de efectos fijos. No se realizaron análisis de subgrupos debido al bajo número de estudios relacionados con los resultados relevantes. Se utilizaron los criterios GRADE para evaluar la calidad de la evidencia.
Resultados principales
Se identificaron 12 ensayos elegibles que reclutaron un total de 746 bebés prematuros. El metanálisis, aunque limitado por la calidad de los datos, mostró un efecto significativo de la SNN en la transición de la alimentación por sonda a la alimentación oral completa (DM ‐5,51 días, IC del 95%: ‐8,20 a ‐2,82; N = 87), la transición del inicio de la alimentación oral a la alimentación oral completa (DM ‐2,15 días, IC del 95%: ‐3,12 a ‐1,17; N = 100), y la duración de la estancia hospitalaria (DM ‐4,59 días, IC del 95%: ‐8,07 a ‐1,11; N = 501). El metanálisis no reveló que la SNN tuviera efectos significativos sobre el aumento de peso. Un estudio encontró que el grupo de SNN tenía un tiempo de tránsito intestinal significativamente más corto durante la alimentación por sonda en comparación con el grupo de control (DM ‐10,50 h, IC del 95%: ‐13,74 a ‐7,26; N = 30). Otros estudios individuales no demostraron ningún efecto positivo claro de la SNN en la edad del lactante en las alimentaciones orales completas, los días desde el nacimiento hasta la lactancia materna completa, las tasas y la proporción de lactantes que se amamantan completamente al ser dados de alta, los episodios de bradicardia ni los episodios de desaturación de oxígeno. Ninguno de los estudios informó ningún resultado negativo. Esos ensayos eran generalmente pequeños y contenían diversas deficiencias metodológicas, como la falta de cegamiento de los evaluadores de la intervención y de los resultados y la variabilidad de las medidas de resultado. La calidad de la evidencia de los resultados evaluados según el GRADE fue baja a muy baja.
Conclusiones de los autores
El metanálisis demostró un efecto significativo de la SNN en la transición de la alimentación por sonda a la alimentación oral completa, la transición del inicio de la alimentación oral a la alimentación oral completa y la duración de la estancia en el hospital. Ninguno de los ensayos informó ningún efecto adverso. Se necesitan estudios bien diseñados y con potenica suficiente que utilicen métodos fiables de asignación al azar, ocultación de la asignación del tratamiento y cegamiento de la intervención y de los evaluadores de resultados. Para facilitar la realización de un metanálisis con estos datos, los futuros estudios que se realicen deben considerar medidas de resultado que sean consistentes con aquellas utilizadas en estudios anteriores.
PICO
Resumen en términos sencillos
Succión no nutritiva para aumentar la estabilidad fisiológica y la nutrición en bebés prematuros
Pregunta de la revisión
¿La succión no nutritiva aumenta la estabilidad fisiológica y la nutrición en lactantes prematuros?
Antecedentes
Un bebé nacido prematuramente puede ser alimentado a través de un tubo en el estómago y a menudo recibe un chupete para chupar para mejorar la nutrición. Un bebé necesita una succión, una deglución y una respiración coordinadas para alimentarse. La capacidad de succionar y tragar está presente a partir de las 28 semanas de gestación pero los lactantes no lo coordinan completamente hasta las semanas 32 o 34. Esto quiere decir que los lactantes prematuros nacidos antes de las 32 semanas de gestación a menudo no pueden alimentarse de forma efectiva del pecho o del biberón. Se les alimenta por una pequeña sonda que se coloca por la nariz hasta le estómago (alimentación por sonda nasogástrica). Succionar un chupete (succión no nutritiva) durante la alimentación por sonda puede fomentar el desarrollo de la conducta de succión y mejorar la digestión de la alimentación. La succión no nutritiva también podría tener efectos calmantes sobre el lactante, aunque también tiene el potencial de interferir con la lactancia materna.
Características de los estudios
Se identificaron 12 ensayos elegibles que reclutaron un total de 746 bebés prematuros en búsquedas actualizadas hasta febrero de 2016.
Resultados clave
Un análisis global sugiere que la succión no nutritiva reduce el tiempo que necesitan los bebés para pasar de la alimentación por sonda a la oral completa y del comienzo de la alimentación oral a la alimentación oral completa. También reduce la duración de la estancia hospitalaria. La succión no nutritiva no mostró un efecto positivo en el aumento de peso.
Calidad de la evidencia
El número de participantes en estos estudios fue pequeño, y se juzgó que la calidad de la evidencia sobre los resultados evaluados era baja o muy baja. Se necesitan grandes ensayos controlados aleatorios bien diseñados para evaluar más a fondo la eficacia y la seguridad de la succión no nutritiva para aumentar la estabilidad fisiológica y la nutrición en los niños prematuros.
Authors' conclusions
Summary of findings
| Non‐nutritive sucking compared with no non‐nutritive sucking for physiologic stability and nutrition | |||||
| Patient or population: preterm infants Settings: neonatal unit Intervention: NNS Comparison: no NNS | |||||
| Outcomes | Anticipated absolute effects (95% CI) * | Relative effect (95% CI) | No of participants | Quality of the evidence | |
| Risk without NNS | Risk with NNS | ||||
| Gavage to full oral feeding (days) | The mean gavage to full oral feeding was 0 days | The mean days from gavage to full oral feeding in the intervention group was 5.51 lower (8.20 lower to 2.82 lower) | — | 87 (2 trials) | ⊕⊕⊝⊝ |
| Start oral feeding to full oral feeding (days) | The mean start oral feeding to full oral feeding was 0 days | The mean days from start of oral feeding to full oral feeding in the intervention group was 2.15 lower (3.12 lower to 1.17 lower) | — | 100 (2 trials) | ⊕⊝⊝⊝ |
| Days from birth to full oral breastfeeding | The mean days from birth to full breastfeeding was 0 days | The mean days from birth to full breastfeeding was 1 day lower (6.71 lower to 4.71 higher) | — | 303 (1 trial) | ⊕⊕⊝⊝ |
| Full breastfeeding at discharge | 520 per 1000 | 0 per 1000 (0 to 0) | Not estimable | 303 (1 trial) | ⊕⊕⊝⊝ |
| Length of hospital stay (days) | The mean length of hospital stay was 0 days | The mean length of hospital stay in the intervention group was 4.59 days lower (8.07 lower to 1.11 lower) | — | 501 (5 trials) | ⊕⊕⊝⊝ |
| Weight gain (g/day) | the mean weight gain 0 grams/day | The mean weight gain in the intervention group was 1.57 g lower (3.5 lower to 0.37 higher) | — | 103 (3 trials) | ⊕⊕⊝⊝ |
| Postconceptual age at full oral feeds (days) | The mean post menstrual age at full oral feeding was 0 days | The mean postconceptual age at full oral feeding in the intervention group was 1.70 days lower (46.06 lower to 42.66 higher) | — | 28 (1 trial) | ⊕⊝⊝⊝ |
| Intestinal transit time (hours) | The mean intestinal transit time was 0 hours | The mean intestinal transit time in the intervention group was 10.50 h lower (13.74 lower to 7.26 lower) | — | 30 (1 trial) | ⊕⊝⊝⊝ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group | |||||
| GRADE Working Group grades of evidence | |||||
| aHigh risk of selection bias. | |||||
Background
Description of the condition
The early components of sucking have been demonstrated to occur in fetal life from about seven to eight weeks postconceptual age. Oral and gag reflexes appear at about 12 to 16 weeks and sucking at 15 to 18 weeks gestation (Breton 2008; Poore 2008). At 28 weeks gestation, some infants may have established a suck‐swallow‐breathe cycle, although they lack the physiological stability to maintain this cycle whilst feeding, which can lead to variable oxygenation, irregular breathing sequence and poor digestion (Jones 2012). The smooth integration of sucking, swallowing and breathing during nutritive feeding allows the infant to feed efficiently and effectively. Full coordination may not occur until 32 to 34 weeks gestation (Amaizu 2008; Goldson 1987; Neiva 2007).This means that preterm infants with less than 32 weeks gestation are usually not able to feed effectively from the breast or a bottle. They are fed by a small tube that is placed up the nose into the stomach (gavage feeding). In the gavage‐fed infant, NNS is extremely important to facilitate a positive association between sucking and swallowing with satiation in order to avoid the development of feed aversion (Barlow 2009; Hawdon 2000). The effect of feeding experience contributes to the development of feeding skills (Amaizu 2008).
The development of both nutritive and non‐nutritive sucking behaviours in preterm infants is thought to reflect neurobehavioral maturation and organization (Lau 2003; Pickler 2009). An organized stable temporal pattern has been identified for both nutritive and non‐nutritive sucking, enabling the features of each to be analysed by quantitative techniques (Wolf 1992). From a clinical perspective, the ability to feed depends on a coordinated sucking, swallowing, and breathing pattern. In preterm infants of less than 32 weeks gestation, this ability is not usually effective enough to sustain full oral feeds (Wolf 1992). In the interim, infants are fed by gavage tube until they are mature enough to take milk directly from the breast or bottle (Greer 2001). The development of oral feeding in infants requires complex anatomical and physiological coordination. The integration of structures involving the lips, cheeks, jaws, tongue, palate, pharynx, and larynx allow for the infant to create the appropriate pressure required for suction and swallowing during oral feeding (Miller 2007). Similarly, the ability to maintain stable physiologic functions such as heart rate, respiratory rate and function, and oxygen saturation are essential to prevent variable oxygenation, bradycardia, and irregular breathing sequence during feeding (Pickler 2004). The coordination of the autonomic, motoric, and behavioral subsystems required to perform these actions may not be fully developed in the preterm infant, resulting in difficulty establishing a stable suck‐swallow‐breathe cycle prior to full‐term gestation (McGrath 2004).The inability of the premature infant to develop a stable suck‐swallow‐breathe cycle can be linked to factors such as poor motor skills and posture, multiple medical complications or an immature autonomic nervous system, which can then be further exacerbated by congenital abnormalities, low birth weight, or developmental complications (Boiron 2007; Dodrill 2008; Miller 2007).
Description of the intervention
Breastfeeding, bottle feeding and cup feeding are considered a form of nutritive sucking (NS) because the purpose of NS is to obtain nutrition in the form of breast milk or formula. Non‐nutritive sucking (NNS) occurs in the absence of nutrient flow and may be used to satisfy an infant's basic sucking urge or as a state regulatory mechanism (Wolf 1992). Pacifiers play a significant role in non‐nutritive sucking, one of which replaces the role of thumb sucking that has been shown to occur in the womb from as early as 12 weeks gestation (Jenik 2009). A gloved finger and empty breast are also described as methods of non‐nutritive sucking (Medeiros 2011).
Most often pacifiers have been used during gavage feeding to facilitate the co‐ordination of sucking and swallowing.The development of the stable suck‐swallow‐breathe cycle present in full term infants is viewed as a sign of neurobehavioral stability and maturation. Hence achieving and maintaining this cycle for preterm infants is often fraught with difficulty, as neural and physiological pathways are often immature and uncoordinated (McGrath 2004). Non‐nutritive sucking has been shown to assist the infant in achieving and maintaining physiological homeostasis and behavioral state (Jenik 2009). During nutritive sucking, if fluid is swallowed incorrectly it can lead to aspiration pneumonia, bradycardia, hypoxia, and fatigue (Crowe 2012; Miller 2007). Non‐nutritive sucking has the ability to create oral feeding experiences without the added stress of fluid. In addition, the act of NNS is one of an infant's first methods of self‐organization and self‐soothing, which is repetitive and rhythmic in nature. Non‐nutritive sucking, particularly with a pacifier, is believed to have a calming effect on infants and is commonly used as an intervention in nurseries and neonatal intensive care units (Kimble 1992b).
How the intervention might work
The rationale for this intervention is that non‐nutritive sucking facilitates the development of sucking behavior and improves digestion of enteral feeds. A number of enzymes/hormones have been implicated in the facilitation of digestion through non‐nutritive sucking: lingual lipase, gastrin, insulin, and motilin. Experts believe that non‐nutritive sucking stimulates the secretion of these enzymes/hormones through vagal innervation in the oral mucosa (Chey 1980; Hamosh 1979; Wiener 1987). NNS use has also been linked to improving the initiation and duration of the first nutritive suck, enhancing weight gain and reducing transition time between gavage and oral feeding (Boiron 2007). Investigators have shown that NNS accelerates the acquisition of mature NNS patterns and improves feeding skills (Barlow 2008).
An improved ability to modulate behavioral state is particularly important for the preterm infant at higher risk of developmental problems. Evidence suggests that providing non‐nutritive sucking opportunities to premature infants during gavage feeding may have beneficial effects on oxygen saturation, gastrointestinal function, growth, and development (Hack 1985). Literature reporting the effectiveness of NNS as a pain relief strategy for infants is also increasing (Tsa 2008).
Why it is important to do this review
Our literature review found a meta‐analysis of five studies of non‐nutritive sucking in preterm infants (Schwartz 1987). The authors concluded that non‐nutritive sucking reduced the time to first bottle feeding and reduced the days of hospitalisation. Outcome data related to weight gain were inconclusive.
A meta‐analysis of the non‐nutritive sucking research in preterm infants by Steer 1992 included eight randomised trials. The major outcome variables studied in these trials included weight gain, gastrointestinal transit, readiness for nipple feedings and length of hospitalisation. Lack of blinding to the intervention or outcome measurement in all studies affected the methodological quality of the findings. The authors concluded that in view of the limitations in the available research, there was insufficient beneficial evidence to support the use of non‐nutritive sucking in the management of tube‐fed preterm infants.
Non‐nutritive sucking within newborn care settings has become common practice. Recent evidence further supports the notion that improving feeding skills through the use of NNS shortens the length of hospital stay (Barlow 2008). As a component of developmentally supportive care, NNS is widely promoted though neonatal intensive care units (NICU) and other newborn care centres. Although commonly considered a benign intervention, further synthesis of the literature is required to support the ongoing use of NNS.
Objectives
To assess the effects of non‐nutritive sucking on physiologic stability and nutrition in preterm infants.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials and quasi‐randomised trials which compared non‐nutritive sucking in preterm infants to no provision of non‐nutritive sucking. We excluded trials evaluating the effect of NNS on pain in preterm infants, and for the 2016 update, we excluded cross‐over trials.
Types of participants
All infants born at less than 37 weeks postconceptual age. We excluded studies involving both preterm and term (greater than or equal to 37 weeks) infants.
Types of interventions
Non‐nutritive sucking involving the use of a pacifier or other method. The intervention can occur before, during or after gavage feeding by a naso/orogastric tube; before or after oral (bottle or breast) feeding; or outside of feeding times.
Types of outcome measures
Primary outcomes
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Time (days) taken to achieve exclusive oral feeding, defined as when the infant ingests all nutrient volumes in a 24 hour period without any gavage (McCain 2001)
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Breastfeeding (at discharge)
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Length of hospital stay (days)
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Weight gain (grams/day) during hospital stay
Secondary outcomes
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Time (days) spent in NICU
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Age of infant (days) at full oral feeding (postmenstrual age or postconceptual age)
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Episodes of bradycardia (during or immediately after feeding) during hospital stay
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Episodes of oxygen desaturation (during or immediately after feeding) during hospital stay
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Activity or behavior (measured during or immediately after feeding by a validated tool, e.g. Brazelton Neonatal Behavioral Assessment Scale, Anderson's Behavioral State Scale) during hospital stay
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Intestinal transit time (hours)
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Neurodevelopmental outcomes at 12 months or more of age (corrected for preterm birth) measured using validated assessment tools such as Bayley Scales of Infant Development, and classifications of disability, including auditory and visual disability. Severe neurodevelopmental disability will be defined as any one or combination of the following: non‐ambulant cerebral palsy, developmental delay (developmental quotient less than 70), auditory and visual impairment
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Any other clinically relevant outcomes as determined by authors
Search methods for identification of studies
Electronic searches
For the 2016 update, we conducted a comprehensive search including: Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1) in The Cochrane Library; MEDLINE via PubMed (1966 to 25 February 2016); Embase (1980 to 25 February 2016); and CINAHL (1982 to 25 February 2016) using the following search terms: ((non‐nutritive AND suck*) OR (nonnutritive AND suck*) OR pacifier OR dummy), plus database‐specific limiters for RCTs and neonates (see Appendix 1 for the full search strategies for each database). We did not apply language restrictions. Additionally, we did not apply any date limits.
We searched clinical trials registries for ongoing or recently completed trials (clinicaltrials.gov; the World Health Organization’s International Trials Registry and Platform www.whoint/ictrp/search/en/, and the ISRCTN Registry).
Searching other resources
We retrieved all potentially relevant titles and abstracts identified during the search. Review authors independently handsearched the bibliographies of each article for additional relevant titles and these were also retrieved. We sent the resulting list of all relevant articles to two major authors in this area and asked them if they knew of any other published or unpublished studies relevant to the area that were not included in the original list.
Data collection and analysis
The systematic review followed the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and by the Cochrane Neonatal Review Group (Higgins 2011).
Selection of studies
Two review authors (JF and TP) screened the title and abstract of all identified studies. We re‐assessed the full text of any potentially eligible reports and excluded the studies that did not meet all of the inclusion criteria. We discussed any disagreements until we achieved consensus.
Data extraction and management
We used the data extraction form available within Review Manager software (RevMan) to extract data on the participants, interventions and control(s), and outcomes of each included trial (RevMan 2014).
Two review authors (JF and KP) independently extracted data from each study without blinding to authorship or journal publication.
In case of any disagreement, two review authors resolved them by discussion until reaching a consensus.
Where data were missing, unclear, or incomplete, we made reasonable attempts to contact the trial authors to obtain the required information.
One review author (JF) entered data into RevMan, and a second review author (KP) verified them (RevMan 2014).
We extracted the following data.
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Participant characteristics.
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Inclusion and exclusion criteria.
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Numbers of enrolled participants and attrition rates (wherever possible).
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Details of intervention.
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Outcomes measured.
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Duration of study and frequency of measurements.
Assessment of risk of bias in included studies
Review authors independently assessed risk of bias for the included studies using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreements successfully by discussion, so it was unnecessary to involve a review arbiter. We completed the 'Risk of bias' table addressing the following methodological domains.
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Selection bias.
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Random sequence generation (biased allocation to interventions) due to inadequate generation of a randomised sequence.
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Allocation concealment: selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment.
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Blinding of participants and personnel: performance bias due to knowledge of the allocated interventions by participants and personnel during the study.
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Blinding of outcome assessment: detection bias due to knowledge of the allocated interventions by outcome assessors.
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Incomplete outcome data: attrition bias due to amount, nature or handling of incomplete outcome data.
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Selective reporting: reporting bias due to selective outcome reporting.
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Other sources of bias: bias due to problems not covered elsewhere in the table.
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Overall bias.
See Appendix 2 for a more detailed description of risk of bias for each domain.
Measures of treatment effect
We performed statistical analyses using RevMan (RevMan 2014). We calculated risk ratios (RR) and risk differences (RD) for dichotomous data, and we analysed continuous data using mean differences (MDs). We reported the 95% confidence interval (CI) on all estimates.
Dealing with missing data
We include additional data obtained from Collins 2004 for the outcomes 'full breastfeeding at discharge and 'days from birth to full breastfeeding'.
Assessment of heterogeneity
We assessed the heterogeneity between the included trials, using the formal and commonly applied statistic to assess heterogeneity: the I2 statistic. This test describes the percentage of total variation observed across studies due to heterogeneity rather than sampling (random) error (Higgins 2011). We graded the degree of heterogeneity as non‐existent or minimal for an I2 value of less than 25%, low for an I2 value of 25% to 49%, moderate for an I2 value of 50% to 74%, and high for an I2 value of 75% to 100%. Had there been evidence of apparent or statistical heterogeneity, we planned to assess the source of the heterogeneity using sensitivity and subgroup analyses looking for sources of bias or methodological differences between the heterogeneous trials (for example, differences in study quality, participants, intervention regimens, or outcome assessments) using post hoc subgroup analyses.
Data synthesis
We performed meta‐analysis using RevMan (RevMan 2014). For estimates of typical risk ratio and risk difference, we used the Mantel‐Haenszel method. For measured quantities, we used the inverse variance method. We used the fixed‐effect model for all meta‐analyses.
Subgroup analysis and investigation of heterogeneity
We did not perform any subgroup analyses because of the small number of studies related to the relevant outcomes.
Summary of findings table
We used the GRADE approach, as outlined in the GRADE Handbook (Schünemann 2013), to assess the quality of evidence for the following (clinically relevant) outcomes: gavage to full oral feeding (days), start oral feeding to full oral feeding (days), days from birth to full breastfeeding, proportion of infants fully breastfeeding at discharge, length of hospital stay, weight gain (grams/day), postconceptual age at full oral feeds and intestinal transit time.
Two review authors (JF and KP) independently assessed the quality of the evidence for each of the outcomes above. We considered evidence from randomised controlled trials as high quality but downgraded it one level for serious (or two levels for very serious) limitations based upon the following: design (risk of bias), consistency across studies, directness of the evidence, precision of estimates and presence of publication bias. We used the GRADEpro 2008 Guideline Development Tool to create a 'Summary of findings' table to report the main findings and the quality of the evidence.
The GRADE approach results in an assessment of the quality of a body of evidence in one of four grades.
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High: we are very confident that the true effect lies close to that of the estimate of the effect.
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Moderate: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
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Low: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
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Very low: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
Results
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies tables.
Results of the search
The search yielded 706 unique records (Figure 1). We included five additional studies in this review update (Collins 2004; Harding 2014a; Lau 2012; Moreira 2014; Zhang 2014).
Study flow diagram: review update
We also found three ongoing RCTs (IRCT201106062324N8; IRCT2013120815458N2; IRCT201501205163N2). See Characteristics of ongoing studies.
Included studies
We describe each study below and in the Characteristics of included studies table.
In total, we included 12 studies (N = 746) in this review: Bernbaum 1983 (N = 30); Collins 2004 (N = 319); Ernst 1989 (N = 18); Field 1982 (N = 57); Gill 1988 (N = 24); Gill 1992 (N = 42); Harding 2014a and Harding 2014b, a single study with two intervention arms (N = 59); Kanarek 1992 (N = 21); Lau 2012 (N = 48); Mattes 1996 (N = 28); Moreira 2014 (N = 40); Zhang 2014 (N = 60). The 12 included trials took place in neonatal centres in North America, the UK, Brazil, China, and Australia.
Participants
Bernbaum 1983 was a single‐centre RCT that included 30 preterm infants with a mean gestational age of 31.5 weeks, weight of less than 1500 grams and mean postnatal age of 10 days. Eligible infants had a birth weight of less than 1500 grams; did not need a surgical intervention or further management from the intensive care team at the time nasogastric feeding commenced; and had no seizures, central nervous system (CNS) haemorrhages or cardiac or pulmonary diseases. The trial excluded infants if they were small for gestational age.
Collins 2004 was a multicentre RCT that included 319 preterm infants with mean birth weight of 1325 grams in the cup and no NNS group, 1508 grams in the bottle no NNS group, 1344 grams in the cup and NNS group, and 1382 g in the bottle and NNS group. Authors did not report postnatal age. Inclusion criteria were women with singleton or twin infants of less than 34 weeks' gestation who wanted to breast feed. The trial excluded infants with congenital abnormalities precluding enteral feeding.
Ernst 1989 was a single‐centre RCT that included 18 preterm infants with mean birth weight 1185 grams in the control group and 1256 grams in the NNS group and a mean gestational age of 29 weeks in the control group and 29 weeks in the NNS group. The study began on day of birth, including infants if they were very low birth weight babies between 890 grams and 1400 grams with an appropriate weight, length, and head circumference for their gestational age (27 to 30 weeks). The trial excluded infants if they experienced seizures or CNS haemorrhage, or if they required surgery, fluid restrictions, prolonged mechanical ventilation, significant supplemental oxygen, discontinued feeding, or formula that was different from the routinely used premature feeding formula.
Field 1982 was a a single‐centre RCT that included 57 infants with a mean birth weight of 1300 grams and mean 32 weeks' gestation. Postnatal age was not reported; however, the study began on day 1. Eligible infants had a birth weight of less than 1800 grams and less than 35 weeks gestational age, and they were free from major congenital abnormalities, chromosomal abnormalities, oropharyngeal problems, and conditions known to be incompatible with life.
Gill 1988 was a single‐centre RCT that included 24 preterm infants with a median birth weight of 1270 grams in the NNS group and 1570 grams in the no NNS group; median gestational age was 30.5 weeks in the NNS group and 31.5 weeks in the no NNS group. Median postnatal age was 19 days in the NNS group and 15 days in the no NNS group. Infants were included if they had a birth weight of less than 2000 grams, gestational age of 34 weeks or less, and appropriate weight for gestational age. They had to be receiving gavage feeding and be ready to have a first bottle feeding. No infants had intraventricular haemorrhage of grades III or IV or congenital or neurological anomalies.
Gill 1992 was a single‐centre RCT that included 42 preterm infants with a mean birth weight of 1254 grams in the control group and 1408 grams in the NNS group, a mean gestational age of 29.3 weeks in the control group and 30.2 weeks in the NNS group, and a mean postnatal age of 25.9 days in the control group and 22.8 days in the NNS group. Infants were included if they weighed under 2000 grams, had a gestational age of 34 weeks or less, had an appropriate weight for gestational age, were being fed by gavage, and were ready to have a first bottle feeding. No infants had intraventricular haemorrhage of grades III or IV or congenital or neurological anomalies.
Harding 2014a (and Harding 2014b) included 59 preterm infants in a single‐centre RCT with two intervention arms. For Intervention 1 (NNS before gavage feeding), the 19 included infants had a mean gestational age of 32.53 weeks and birth weight of 1651 grams, and for intervention 2 (NNS during gavage feeding) the 20 included infants had a mean gestational age of 31.60 weeks and a mean birth weight of 1651 grams. The control group had a mean gestational age of 30.95 weeks and mean birth weight of 1676 grams. Authors did not report postnatal age, but the trial included infants when they started to show oral readiness. They were eligible if they were preterm and excluded if they were identified as having congenital disorders, intraventricular haemorrhages III or IV, severe respiratory problems, or necrotizing enterocolitis.
Kanarek 1992 was a single‐centre RCT that included 21 preterm infants with a mean birth weight of 1450 grams in the control group and 1320 grams in the NNS group, a mean gestational age of 31.8 weeks in the control group and 31.0 weeks in the NNS group, and postnatal age of one day. The trial included infants if their weight was appropriate for gestational age and if they were free from major congenital abnormalities, perinatal asphyxia, infection and respiratory distress.
Lau 2012 included infants with a mean birth weight of 1121 grams in the control group and 1076 grams in the NNS group and with a mean gestational age of 28.1 weeks in both groups. Mean postmenstrual age was 38.8 weeks in the control group and 39.0 weeks in the NNS group. The trial is a single‐centre RCT and included infants identified as 'feeders and growers' with a primary diagnosis of prematurity, and it excluded infants if they had gastrointestinal complications, congenital anomalies or chronic medical conditions: intraventricular haemorrhage grade III and IV, periventricular leukomalacia, necrotizing enterocolitis or bronchopulmonary dysplasia.
Mattes 1996 was a multicenter RCT that included 28 preterm infants with a mean birth weight of 1321 grams in the control group and 1377 grams in the NNS group, a mean gestational age of 30.5 weeks in the control group and 31.1 weeks in the NNS group, and a mean postconceptual age of 33.7 weeks in the control group and 33.6 weeks in the NNS group. The trials included infants if their body weight was 1250 grams or more, had a gestational age of less than 34 weeks, had growth parameters appropriate for gestational age, Apgar scores of more than 3 at one minute and more than 5 at five minutes, no clinical evidence of seizure activity or grade III or IV intraventricular haemorrhage, no congenital heart disease other than patent ductus arteriosus or peripheral pulmonic stenosis that was haemodynamically significant, and no respiratory distress syndrome. Excluded from the study were infants with signs of necrotizing enterocolitis, hepatic disorder, congenital infection, metabolic disease, or anomalies affecting the central nervous system or gastrointestinal tract.
Moreira 2014 was a single‐centre RCT that included 40 preterm infants with a birth weight of 1256 grams in the control group and 1306 grams in the NNS group and a mean gestational age of 29.9 weeks in the control group and 30.1 weeks in the NNS group. Authors did not report postnatal age. The study included infants if they had a birth weight of less than 1500 grams, gestational age at birth of 32 weeks or less, five‐minute Apgar score of 6 or more, clinical (respiratory and haemodynamic) stability on enrolment and during the study, initiation of enteral feeding by oral or nasogastric tube associated or not with parenteral nutrition. Exclusion criteria were infants with grades III/IV intraventricular haemorrhage, clinical instability on enrolment or during the study, including necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia and other clinical respiratory or haemodynamic instabilities, five‐minute Apgar score of 5 or less, presence of genetic syndromes, neurological disorders, or head, neck or central nervous system congenital malformations.
Zhang 2014 was a single‐centre RCT that included 55 preterm infants. Infants in the NNS group had a mean birth weight of 1548 grams and mean gestational age of 30.9 weeks, and infants in the control group had a mean birth weight of 1651 grams and a mean gestational age of 31.1 weeks. The trial is a single‐centre RCT. Postnatal age was not reported, but all included infants were born in other hospitals and transported within 24 hours to 48 hours to the NICU. The trial included infants born at 29 to 34 weeks gestation, who had an appropriate weight for gestational age, Apgar scores of more than 3 at one minute and more than 5 at at five minutes, and who received all feedings by tube. The trial excluded infants with congenital abnormalities (oral, heart etc.) and infants who developed chronic medical complications during NICU admission such as intraventricular haemorrhage grades III and IV, bronchopulmonary dysplasia, or necrotizing enterocolitis.
Interventions
The NNS intervention was via a pacifier in all but one study, which used a gloved finger (Moreira 2014). There was substantial variability as to when and how the NNS was used. Non‐nutritive sucking occurred before gavage feeding (Harding 2014a; Moreira 2014; Zhang 2014), during gavage feeding (Bernbaum 1983; Field 1982; Harding 2014b; Mattes 1996), during and after gavage feeding (Ernst 1989; Kanarek 1992), before bottle feeding (Gill 1988; Gill 1992), or not directly related to feeding (Collins 2004; Lau 2012).
NNS before gavage feeding
Harding 2014a reported on NNS prior to gavage feeding. Parents were encouraged to use a pacifier to elicit three sequential sucks and to encourage sequential sucking for a minimum of five minutes. Infants received the intervention after they started showing signs of oral readiness. The intervention lasted a minimum of three days until they were taking all of their feeds orally. Moreira 2014 reported on the use of NNS with gloved finger for 10 minutes, three times a day for three days a week before gavage feeding. Zhang 2014 reported on the use of NNS, and NNS and oral stimulation 30 minutes prior to gavage feeding. Infants in the NNS group were allowed to suck on pacifiers for five minutes, 7 to 8 times a day (Zhang 2014). The pacifier was placed in the infant's mouth whether or not they made an attempt to suck; however, where necessary the nurse would manipulate the pacifier to encourage sucking.
NNS during gavage feeding
Bernbaum 1983 reported on NNS during gavage feeding, where infants did not have sucking opportunities between feeding periods. The pacifier, which was constructed from an unperforated standard‐sized disposable nipple plugged with the plunger of a 20 mL syringe to prevent swallowing of air, was manipulated to encourage sucking and was placed so that it remained in the infant's mouth during the entire feeding. All infants were gavage fed until they attained a weight of 1700 grams, at which time they began oral feedings that advanced in frequency and amount according to the infant's tolerance. Field 1982 reported on NNS during gavage feeding, in which infants were given the pacifiers whether or not they made an effort to suck. Infants in both groups were allowed to have a pacifier at any other time, but only the treatment group received the pacifier during gavage feeding. Infants began bottle feeding when they weighed 1500 grams and their medical condition was stable. Harding 2014b reported on NNS during gavage feeding, whereby parents were encouraged to use a pacifier to elicit three sequential sucks and to encourage sequential sucking for a minimum of five minutes. Infants received the intervention after they started showing signs of oral readiness. The intervention was provided for a minimum of three days until they were taking all of their feeds orally. The study did not describe the pacifier used for the study. Mattes 1996 reported NNS during gavage feeding whereby infants were provided a standard latex pacifier during all feedings until they were able to tolerate full oral feedings.
NNS during and after gavage feeding
Ernst 1989 reported on NNS during and after gavage feeding, in which infants received a pacifier constructed from a standard blue premature nipple, stuffed with gauze for resistance and attached with tape to a rolled terry cloth for each of manipulation and positioning in the infant's mouths, with each feeding. Pacifiers were positioned in the mouth throughout and after and maintained in the mouth throughout and after the feeding for a total of 30 minutes. Manipulation of the pacifier in the infant's mouth and stroking of the infant's cheek were used to stimulate NNS when infants stopped sucking during each 30 minute treatment. The treatment phase of the study ended when infants weighed approximately 1700 grams, gavage feedings were discontinued, and all infants began nipple feedings. Kanarek 1992 reported on NNS during and after gavage feeding, whereby infants received a commercial pacifier beginning on the first day of life, during and after all feedings and when they were awake. Blood measurements were taken before and 72 hours after the initiation of continuous gavage feedings. In infants who were bolus‐fed, investigators obtained the second specimen 20 minutes after the feed.
NNS before bottle feeding
Gill 1988 reported on the use of NNS five minutes before bottle feeding every three hours for the first 48 hours. The trial used two sizes of 'firm slow‐feed' commercial nipples as pacifiers by inserting the distal end of a plastic disposable 3 mL syringe cover into the nipple as a prop and to block air entry. When necessary, nurses cut the nipple flat on one side to facilitate entry into the infant's mouth. Gill 1992 reported on the use of NNS, using commercial bottle nipples that varied in size and firmness but matched the nipple being used for bottle feedings, five minutes before bottle feeding every three hours and beginning with the first bottle feed, for the first 48 hours. The infant received a pacifier that was kept in the infant's mouth, whether or not sucking occurred.
NNS not directly related to feeding
Lau 2012 reported on a sucking exercise that consisted of NNS with the commercial pacifiers that were routinely used in the NICU. This was achieved by gently moving the pacifier in a rhythmic up/down motion that stimulated the NNS. All infants received the use of the pacifier, but only infants in the NNS group received this exercise. Experienced research feeding therapists provided NNS between, but not within the 30 minutes prior to oral feedings, 15 minutes per day, five days a week.
Collins 2004 reported on the use of bottle/cup feeding and NNS and bottle/cup feeding and no NNS. Infants in the experimental group received a dummy in between feeds. Cup or bottle feeding commenced at the discretion of the attending nurse/midwife or neonatologist and occurred when the mother was unavailable to breast feed or when additional milk, given orally, was required after a breast feed. Investigators used small plastic medicine cups. Infants randomised to NNS groups had dummies available on trial entry; their use was encouraged during tube feeds and when the infant was restless. Infants received NNS between feeds when needed.
Outcomes
The 12 studies used a large number of outcomes, but only a few were common among them. In addition, there was considerable variability or lack of reporting in relation to how and when the outcomes were measured.
Bernbaum 1983 reported on intraoral negative (sucking) pressures, sucking patterns, daily caloric intake, anthropometric measures (weight, length, and head circumference), gastrointestinal transit time, frequency of bowel movements, time taken until first five bottle feeds were achieved, time to reach 2000 grams weight, days for transition from partial to full oral feeds, and length of hospital stay. Collins 2004 reported on the proportion of infants fully breastfeeding (compared with partially and not) at discharge, days from birth to full breastfeeding, and length of hospital stay.
Ernst 1989 reported on anthropometric measures (weight, length, head and arm circumferences, and subscapular and triceps skin folds), gastrointestinal transit time, description and frequency of stools, amount of aspirated gastric residue, serum protein determinations, energy expenditure, energy and fat excretions/energy expenditure, and total caloric value. Field 1982 reported on number of days of tube feedings, number of tube feeds, weight, length of hospital stay, cost of hospital stay, behavioral assessment, and feeding behaviours, including incidence of regurgitation, volume of formula intake and length of feeding time. Gill 1988 and Gill 1992 reported on behavioral state. Harding 2014a and Harding 2014b reported on time taken to achieve full oral feeding, number of days in hospital, type of sucking pattern, and average age of gestation for oral feeding. They also reported number of re‐admissions, difficulties with oral feeding, and receptive and expressive language ratings at follow‐up. Kanarek 1992 reported on gastrin, motilin, insulin, and insulin‐like growth factor‐1 concentrations. Lau 2012 reported on days from start to independent oral feedings, feeding performance, volume taken at five minutes, volume taken during entire feeding, and duration of oral feeding. Mattes 1996 reported on anthropometric measurements (body weight, length, head circumference, midarm circumference, triceps skinfold, subscapular skinfold), sucking measures and age at full oral feeds. Moreira 2014 reported on readiness to commence suck feeds, transition time to oral feeding, exclusive maternal breastfeeding, and occurrence of distress signals. Zhang 2014 reported on number of days transitioning from introduction of oral feeding to autonomous oral feeding, rate of milk transfer, feeding proficiency, volume transfer, weight gain, length of hospital stay, behavioral state, episodes of apnoea, bradycardia, and oxygen desaturation.
Excluded studies
See Characteristics of excluded studies.
We excluded a total of 38 studies from the review (Barlow 2014a; Barlow 2014b; Bingham 2003; Burroughs 1981; Burroughs 1978; Cevasco 2005; Corvaglia 2016; Daniels 1988; De Curtis 1986; DiPietro 1994; Gilliam 2011; Jaafar 2011; Kamhawy 2014; Kimble 1992a; Kronborg 2009; Marchini 1987; McCain 1992; McCain 1995; Measel 1979; Miller 1993; Narayanan 1991; Neeley 1979; Orenstein 1988; Paludetto 1984; Paludetto 1986; Pickler 1993; Pickler 1996; Pickler 2004; Pimenta 2008; Sehgal 1990; Song 2014; Standley 2003; Szabo 1985; Widstrom 1988; Woodson 1985; Woodson 1988; Yildiz 2012; Yu 1999). The reason for exclusion in all cases was because they did not meet one or more of the inclusion criteria.
Risk of bias in included studies
Generally, the trials poorly described the randomisation methods, allocation concealment and blinding of personnel and outcome assessors. We present details of the methodological quality assessments in the Characteristics of included studies table. We completed a 'Risk of bias' table for each eligible study, and our overall assessment of risk of bias using a 'Risk of bias' graph (Figure 2) and 'Risk of bias' summary (Figure 3).
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Seven of the 12 RCTs were at low risk of bias for allocation concealment (Bernbaum 1983; Collins 2004; Gill 1988; Gill 1992; Harding 2014a; Kanarek 1992; Mattes 1996).
Blinding
Only one study was at low risk of bias for blinding of participants or personnel to the intervention and blinding of outcome assessors (Zhang 2014).
Incomplete outcome data
All 12 included studies were at low risk of bias for incomplete outcome data. Non‐adherence to the intervention was high in Collins 2004. Of the infants randomised to no dummy, 31% (47/152) had a dummy introduced, usually because the baby was unsettled (37%, 14/38) or caregivers wanted to teach the baby to suck (29%, 11/38). We analysed data as intention‐to‐treat.
Selective reporting
Protocols (or trials registration material) were unavailable for the majority of included studies.
Effects of interventions
Primary outcomes
Time (days) taken to achieve exclusive oral feeding
Three studies reported on transition from gavage to full oral feeding (days) (Bernbaum 1983; Field 1982; Moreira 2014). We were able to include two studies in the meta‐analysis (Bernbaum 1983; Field 1982), and we found a statistically significant reduction in transition from gavage to full oral feeding in the NNS group (MD −5.51 days, 95% CI −8.20 to −2.82; N = 87; I2 = 0%; Analysis 1.1; low‐quality evidence).
Moreira 2014 also reported on the transition from gavage feeding to bottle feeding, finding a significant decrease in transition time in the group receiving NNS prior to gavage feeding compared to the control group (3 days versus 5 days, P = 0.001).
Lau 2012 and Zhang 2014 reported on transition from start of oral feeding to full oral feeding and found a statistically significant reduction in NNS group (during, and before gavage feeding) compared to the control group (MD −2.15 days, 95% CI −3.12 to −1.17; N = 100; Analysis 1.2; very low‐quality evidence); however, the I2 value of 59% indicated moderate heterogeneity.
Collins 2004 reported on days from birth to full breastfeeding and found no difference between the NNS and no NNS groups (MD −1.00 days, 95% CI −6.71 to 4.71; N = 303; Analysis 1.3; low‐quality evidence). The trial defined breastfeeding as mother's milk given by direct breastfeeding or other feeding device.
Full breastfeeding at discharge
Collins 2004 reported on the proportion of infants fully breastfeeding at discharge and found no difference between the NNS and no NNS groups (typical RR 1.08, 95% CI 0.88 to 1.33; typical RD 0.04, 95% CI −0.07 to 0.16, N = 303; Analysis 1.4; low‐quality evidence). The trial defined breastfeeding as mother's milk given by direct breastfeeding or other feeding device.
Moreira 2014 also reported no statistical difference between the the NNS and control groups in rates of exclusive maternal breastfeeding on hospital discharge (P = 0.41).
Length of hospital stay (days)
Five trials examined the effect of NNS on length of hospital stay (in days) and contributed data to the meta‐analysis (Bernbaum 1983; Collins 2004; Field 1982; Harding 2014a (Harding 2014b); Zhang 2014). These trials used NNS before or during gavage feeding. Meta‐analysis showed a statistically significant shorter length of hospital stay for infants in the NNS compared to the control infants (MD −4.59 days, 95% CI −8.07 to −1.11; N = 501; Analysis 1.5; low‐quality evidence).The I2 statistic of 19% indicated minimal heterogeneity.
Weight gain (grams/day)
Five trials reported the effect of NNS on weight gain (Bernbaum 1983; Ernst 1989; Field 1982; Mattes 1996; Zhang 2014). We could include three randomised trials in the meta‐analysis (Ernst 1989; Field 1982; Mattes 1996), which showed no significant difference between the NNS and control groups (MD −1.57 grams/day, 95% CI −3.50 to 0.37; N = 103; Analysis 1.6; low‐quality evidence) and with an I2 statistic of 0% indicating no heterogeneity.
Bernbaum 1983 found a significant difference in weight gain favouring the NNS (during gavage feeding) group by the second week, and the difference remained significant throughout the six‐week study period. We did not include this study in the meta‐analysis because the standard deviations were unavailable from the authors. Zhang 2014 reported the average weight gain rate (%) and found no difference in weight at independent oral feeding between the NNS, NNS plus oral stimulation, and control groups. Based on the results of the studies, there is no clear benefit of NNS with respect to weight gain.
Secondary outcomes
Time (days) spent in NICU
Time spent in NICU was not reported in any of the included studies.
Age of infant at full oral feeding
Lau 2012 found no significant difference between the NNS (not directly related to feeding) and control groups for postmenstrual age at full oral feeding (MD −0.10 days, 95% CI −0.36 to 0.16; N = 48; Analysis 1.7).
Mattes 1996 similarly found no difference between the NNS (during gavage feeding) and control groups for postconceptual age at full oral feeds (MD −1.70 days, 95% CI −46.06 to 42.66; N = 28; Analysis 1.8; low‐quality evidence).
Episodes of bradycardia
Zhang 2014 reported no significant difference in bradycardia between the NNS and control groups. No data was provided by the authors.
Episodes of oxygen desaturation
Zhang 2014 reported no significant difference in oxygen desaturations between the NNS and control groups. No data was provided by the authors.
Behavioral state
Four studies reported on behavioral state; however, we were unable to combine the results due to the method of reporting and therefore report them in narrative form. Zhang 2014 used the Anderson 12‐level Behavioral State Scale and reported no difference in behavioral state between NNS (given before gavage feedings) and control groups. Field 1982 used the Brazelton Neonatal Behavioral Assessment Scale (NBAS) and found that NNS during gavage feeding had no effect on behavioral state. Gill 1988 used the Anderson 12‐level Behavioral State Scale and reported that the most frequent transition was from quiet sleep to drowsy for NNS (before bottle feeding) and from quiet sleep to restless awake in the control group. Gill 1992 also used the Anderson 12‐level Behavioral State Scale and found sleep states occurred more frequently in the NNS (before bottle feeding) group, and restless states were twice as frequent in the control group.
Intestinal transit time
Bernbaum 1983 reported on intestinal transit time and found that the NNS group (during gavage feeding) had a significantly shorter intestinal transit time compared to the control group (MD −10.50 hours, 95% CI −13.74 to −7.26; N = 30; Analysis 1.9; very low‐quality evidence).
Ernst 1989 reported no effect of NNS on gastric emptying (during and after gavage feeding), but no data were available for this trial. Kanarek 1992 studied the effect of NNS in gavage‐fed infants on specific hormones and found NNS (during and after gavage feeding) to have no apparent effect on the blood concentrations of motilin, gastrin, insulin, or insulin‐like growth factor‐1 three days after commencing feeds.
Neurodevelopmental outcomes
No studies reported on neurodevelopmental outcomes.
Discussion
Summary of main results
Meta‐analysis demonstrated a significant effect favouring NNS on transition from gavage to full oral feeding (days), transition from start of oral feeding to full oral feeding (days), the length of hospital stay (days) and intestinal transit time. We found no significant effect for NNS on weight gain. One study found that NNS (during gavage feeding) significantly shortened intestinal transit time. Other individual studies demonstrated no clear positive effect of NNS on age of infant at full oral feeds, days from birth to full breastfeeding, rates and proportion of infants fully breastfeeding at discharge, episodes of bradycardia, and episodes of oxygen desaturation. The evidence for a positive effect on infant behavioral state is inconclusive, with two studies reporting that NNS had no effect on behavioral state and two studies reporting positive effects on sleep states. One study reported that NNS had no apparent effect on motilin, gastrin, insulin, or insulin‐like growth factor‐1. None of the studies reported any negative outcomes.Meta‐analysis demonstrated a significant effect of NNS on transition from gavage to full oral feeding (days), transition from start of oral feeding to full oral feeding (days), and the length of hospital stay (days). Meta‐analysis revealed no significant effect of NNS on weight gain. Individual studies demonstrated no clear positive effect of NNS on age of infant at full oral feeds, days from birth to full breastfeeding, rates and proportion of infants fully breastfeeding at discharge, episodes of bradycardia or episodes of oxygen desaturation. The evidence for positive effect on infant behavioral state is not consistent, with two studies reporting that NNS had no effect on behavioral state and two studies reporting positive effects on sleep states. One study found that NNS decreased intestinal transit time, and one study reported that NNS had no apparent effect on motilin, gastrin, insulin, or insulin‐like growth factor‐1. None of the studies reported any negative outcomes. The studies range in size but are mainly small and often poorly designed, particularly the earlier studies. Readers should interpret study results with caution and consider methodological limitations.
Quality of the evidence
The quality of the evidence ranged from low to very low according to the GRADE approach for all of the major outcomes. Moreover, few trials contributed to meta‐analyses of the primary outcomes, and most of the trials that did not provide numerical data did not demonstrate any effect for NNS.
There were a number of limitations on the presently available evidence.
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Design limitations. Because of the nature of the intervention, blinding of the intervention only occurred in 1 of the 12 studies. Likewise, blinding of outcome assessors, although possible, was evident in only one of the studies reviewed.
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Outcome variability. Meta‐analysis was limited in this review due to the large variation in outcomes and the limited number of randomised trials that were included in each outcome. Although many of the studies measured similar outcomes, the outcomes were too dissimilar to be included in a meta‐analysis. Alternatively, the authors reported the significance level but did not provide specific data. In addition, the context of the measurement of the outcomes varied greatly among studies. For example, investigators measured outcomes before, during or after gavage feeding; before or after bottle feeding; separately from feeding; with variable timing; or they did not report the timing. Because of the small number of studies in each category that measured comparable outcomes, we combined all studies regardless of context. However, readers should consider these contextual differences when interpreting the results of the review.
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Lack of long‐term data. The studies reviewed included no short‐ or long‐term negative outcomes. The outcomes that trialists chose showed either a positive short‐term effect or no effect as a result of NNS. None of included studies reported on long‐term developmental outcomes in the infants.
Despite limiting the included studies to randomised controlled trials and quasi‐randomised trials in this update of the systematic review, the certainty of the conclusions was not strengthened due to the methodological limitations of the included studies. Therefore, readers should interpret the study results with caution.
Agreements and disagreements with other studies or reviews
The findings from this review are consistent with the findings of three earlier systematic reviews (Premji 2000; Schwartz 1987; Steer 1992). Premji 2000 synthesized eight randomized trials and concluded that NNS reduced length of hospitalisation but its effects on sucking response, gastric emptying and weight gain were inconclusive. Schwartz 1987 synthesized five studies of non‐nutritive sucking in preterm infants in a meta‐analysis. The authors concluded that non‐nutritive sucking reduced the time to first bottle feeding and reduced the days of hospitalisation. Outcome data related to weight gain were inconclusive. A meta‐analysis of the non‐nutritive sucking research in preterm infants by Steer, Lucas and Sinclair (Steer 1992) included eight randomised trials. The major outcome variables studied in these trials included weight gain, gastrointestinal transit, readiness for nipple feedings and length of hospitalisation. A lack of blinding to the intervention and/or outcome measurement in all studies affected the methodologic quality of the findings. The authors concluded that in view of the limitations in the available research, there was insufficient beneficial evidence to support the use of non‐nutritive sucking in the management of tube‐fed preterm infants.
Study flow diagram: review update
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 1 Gavage to full oral feeding (days).
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 2 Start of oral feeding to full oral feeding (days).
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 3 Days from birth to full breastfeeding.
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 4 Full breastfeeding at discharge.
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 5 Length of hospital stay (days).
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 6 Weight gain (grams/day).
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 7 Postmenstrual age at full oral feeding.
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 8 Postconceptual age at full oral feeds (days).
Comparison 1 Non‐nutritive sucking vs control in premature infants, Outcome 9 Intestinal transit time (hours).
| Non‐nutritive sucking compared with no non‐nutritive sucking for physiologic stability and nutrition | |||||
| Patient or population: preterm infants Settings: neonatal unit Intervention: NNS Comparison: no NNS | |||||
| Outcomes | Anticipated absolute effects (95% CI) * | Relative effect (95% CI) | No of participants | Quality of the evidence | |
| Risk without NNS | Risk with NNS | ||||
| Gavage to full oral feeding (days) | The mean gavage to full oral feeding was 0 days | The mean days from gavage to full oral feeding in the intervention group was 5.51 lower (8.20 lower to 2.82 lower) | — | 87 (2 trials) | ⊕⊕⊝⊝ |
| Start oral feeding to full oral feeding (days) | The mean start oral feeding to full oral feeding was 0 days | The mean days from start of oral feeding to full oral feeding in the intervention group was 2.15 lower (3.12 lower to 1.17 lower) | — | 100 (2 trials) | ⊕⊝⊝⊝ |
| Days from birth to full oral breastfeeding | The mean days from birth to full breastfeeding was 0 days | The mean days from birth to full breastfeeding was 1 day lower (6.71 lower to 4.71 higher) | — | 303 (1 trial) | ⊕⊕⊝⊝ |
| Full breastfeeding at discharge | 520 per 1000 | 0 per 1000 (0 to 0) | Not estimable | 303 (1 trial) | ⊕⊕⊝⊝ |
| Length of hospital stay (days) | The mean length of hospital stay was 0 days | The mean length of hospital stay in the intervention group was 4.59 days lower (8.07 lower to 1.11 lower) | — | 501 (5 trials) | ⊕⊕⊝⊝ |
| Weight gain (g/day) | the mean weight gain 0 grams/day | The mean weight gain in the intervention group was 1.57 g lower (3.5 lower to 0.37 higher) | — | 103 (3 trials) | ⊕⊕⊝⊝ |
| Postconceptual age at full oral feeds (days) | The mean post menstrual age at full oral feeding was 0 days | The mean postconceptual age at full oral feeding in the intervention group was 1.70 days lower (46.06 lower to 42.66 higher) | — | 28 (1 trial) | ⊕⊝⊝⊝ |
| Intestinal transit time (hours) | The mean intestinal transit time was 0 hours | The mean intestinal transit time in the intervention group was 10.50 h lower (13.74 lower to 7.26 lower) | — | 30 (1 trial) | ⊕⊝⊝⊝ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group | |||||
| GRADE Working Group grades of evidence | |||||
| aHigh risk of selection bias. | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Gavage to full oral feeding (days) Show forest plot | 2 | 87 | Mean Difference (IV, Fixed, 95% CI) | ‐5.51 [‐8.20, ‐2.82] |
| 2 Start of oral feeding to full oral feeding (days) Show forest plot | 2 | 100 | Mean Difference (IV, Fixed, 95% CI) | ‐2.15 [‐3.12, ‐1.17] |
| 3 Days from birth to full breastfeeding Show forest plot | 1 | 303 | Mean Difference (IV, Fixed, 95% CI) | ‐1.0 [‐6.71, 4.71] |
| 4 Full breastfeeding at discharge Show forest plot | 1 | 303 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.88, 1.33] |
| 5 Length of hospital stay (days) Show forest plot | 6 | 501 | Mean Difference (IV, Fixed, 95% CI) | ‐4.59 [‐8.07, ‐1.11] |
| 6 Weight gain (grams/day) Show forest plot | 3 | 103 | Mean Difference (IV, Fixed, 95% CI) | ‐1.57 [‐3.50, 0.37] |
| 7 Postmenstrual age at full oral feeding Show forest plot | 1 | 48 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.36, 0.16] |
| 8 Postconceptual age at full oral feeds (days) Show forest plot | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | ‐1.70 [‐46.06, 42.66] |
| 9 Intestinal transit time (hours) Show forest plot | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | ‐10.5 [‐13.74, ‐7.26] |
