CD 006072

Effect of taurine supplementation on growth and

development in preterm or low birth weight infants (Review)

Verner AM, McGuire W, Craig JS

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

2010, Issue 11

http://www.thecochranelibrary.com

Effect of taurine supplementation on growth and development in preterm or low birth weight infants (Review)

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 1 Growth during trial

period. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Analysis 1.2. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 2 Intestinal fat

absorption (percentage of total intake). . . . . . . . . . . . . . . . . . . . . . . . . . 19

Analysis 1.3. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 3 Electroretinography. 20

Analysis 1.4. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 4 Auditory brainstem-

evoked responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Analysis 1.5. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 5 Neonatal mortality. 22

Analysis 1.6. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 6 Incidence of

necrotising enterocolitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

22WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

24INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iEffect of taurine supplementation on growth and development in preterm or low birth weight infants (Review)


[Intervention Review]

Effect of taurine supplementation on growth anddevelopment in preterm or low birth weight infants

Alison M Verner2, William McGuire1, John Stanley Craig3

1Centre for Reviews and Dissemination, Hull York Medical School, York, UK. 2Regional Neonatal Unit, Royal Maternity Hospital,

Belfast, UK. 3Regional Neonatal Unit, Royal Maternity Hospital, Belfast, Ireland

Contact address: William McGuire, Centre for Reviews and Dissemination, Hull York Medical School, University of York, York, Y010

5DD, UK. [email protected].

Editorial group: Cochrane Neonatal Group.

Publication status and date: Edited (no change to conclusions), published in Issue 11, 2010.

Review content assessed as up-to-date: 19 July 2007.

Citation: Verner AM, McGuire W, Craig JS. Effect of taurine supplementation on growth and development in

preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD006072. DOI:

10.1002/14651858.CD006072.pub2.


A B S T R A C T

Background

Taurine is the most abundant free amino acid in breast milk. Evidence exists that taurine has important roles in intestinal fat absorption,

hepatic function, and auditory and visual development in preterm or low birth weight infants. Observational data suggest that relative

taurine deficiency during the neonatal period is associated with adverse long-term neurodevelopmental outcomes in preterm infants.

Current standard practice is to supplement formula milk and parenteral nutrition solutions with taurine.

Objectives

To assess the effect of providing supplemental taurine for enterally or parenterally fed preterm or low birth weight infants on growth

and development.

Search methods

The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central

Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - June 2007), EMBASE (1980 -

June 2007), conference proceedings, and previous reviews.

Selection criteria

Randomised or quasi-randomised controlled trials that compared taurine supplementation versus no supplementation in preterm or

low birth weight newborn infants.

Data collection and analysis

Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and

data extraction by two review authors, and synthesis of data using relative risk, risk difference and weighted mean difference.

1Effect of taurine supplementation on growth and development in preterm or low birth weight infants (Review)


mailto:[email protected]

Main results

Nine small trials were identified. In total, 189 infants participated. Most participants were greater than 30 weeks gestational age at birth

and were clinically stable. In eight of the studies, taurine was given enterally with formula milk. Only one small trial assessed parenteral

taurine supplementation. Taurine supplementation increased intestinal fat absorption [weighted mean difference 4.0 (95% confidence

interval 1.4, 6.6) percent of intake]. However, meta-analyses did not reveal any statistically significant effects on growth parameters

assessed during the neonatal period or until three to four months chronological age [rate of weight gain: weighted mean difference -

0.25 (95% confidence interval -1.16, 0.66) grams/kilogram/day; change in length: weighted mean difference 0.37 (95% confidence

interval -0.23, 0.98) millimetres/week; change in head circumference: weighted mean difference 0.15 (95% confidence interval -0.19,

0.50) millimeters/week]. There are very limited data on the effect on neonatal mortality or morbidities, and no data on long-term

growth or neurological outcomes.

Authors’ conclusions

Despite that lack of evidence of benefit from randomised controlled trials, it is likely that taurine will continue to be added to formula

milks and parenteral nutrition solutions used for feeding preterm and low birth weight infants given the putative association of taurine

deficiency with various adverse outcomes. Further randomised controlled trials of taurine supplementation versus no supplementation

in preterm or low birth weight infants are unlikely to be viewed as a research priority, but there may be issues related to dose or duration

of supplementation in specific subgroups of infants that merit further research.

P L A I N L A N G U A G E S U M M A R Y

Effect of taurine supplementation on growth and development in preterm or low birth weight infants

Taurine is an amino acid that helps infants absorb fat from the gastrointestinal tract and ensures that the liver deals with waste products

efficiently. Taurine may also have important roles in protecting nerves from damage, especially in the eyes and ears. This review sought

evidence that supplementing the diet of preterm and low birth weight infants with taurine improves their growth and development.

Nine small trials were found, but these did not provide any evidence that providing extra taurine improved outcomes. However, further

trials of taurine supplementation are not likely to take place since taurine is naturally present in breast milk and current standard

practice is to add taurine to formula milk and to intravenous nutrition solutions for feeding preterm and low birth weight infants.

B A C K G R O U N D

Taurine, the major intracellular free amino acid in humans, is con-

sidered “conditionally essential” since needs are not met when in-

take is low (Sturman 1995). Preterm infants are especially depen-

dent on an adequate dietary intake to maintain plasma taurine lev-

els because renal immaturity limits tubular reabsorption and low

hepatic cystathionase activity limits biosynthesis (Sturman 1980).

Taurine is not incorporated into protein. There is no distinct clin-

ical phenotype associated with taurine deficiency in preterm in-

fants. However, several lines of evidence suggest that taurine is

important for growth and development (Chesney 1998a; Chesney

1998b).

The concentration of taurine is highest in neural tissue, particu-

larly in the developing brain. Taurine is an important intracellular

osmolyte that helps regulate the volume of neurons in response

to osmotic changes (Massieu 2004; Trachtman 1988; Trachtman

1990). Taurine also has antioxidant and membrane stabilising

properties that may be important in preventing tissue injuries

such as periventricular haemorrhage, retinopathy of prematurity,

chronic lung disease, or necrotising enterocolitis in preterm in-

fants (Thibeault 2000). An observational study has found a corre-

lation between low plasma taurine levels in early infancy and poor

developmental outcome in preterm infants (Wharton 2004).

Evidence exists that taurine is important for visual and auditory

development. In neonatal animal models, taurine deficiency is as-

sociated with retinal abnormalities (Hayes 1975; Imaki 1993).

Children who receive prolonged parenteral nutrition without tau-

rine develop electroretinographic abnormalities that resolve when

their taurine deficiency is corrected (Geggel 1985; Ament 1986).

Taurine is found at high concentrations in the inner ear (Horner

1997). Newborn kittens of cats who received supplemental taurine



demonstrate earlier brainstem auditory evoked response matura-

tion than kittens of cats who had not received supplemental taurine

(Vallecalle 1991). However, studies in term human infants suggest

that relative taurine deficiency is associated with the development

of more rapid auditory brainstem responses and that lower taurine

levels aid auditory synaptic maturation (Dhillon 1998). Addition-

ally, taurine and aminoglycosides have synergistic ototoxic effects

in some animal models (Kay 1990).

Taurine conjugates with bile acids to form bile salts that are needed

for fatty acid absorption. Although glycine can also conjugate with

bile acids, taurine conjugates predominate in human milk fed

preterm infants during early infancy (Watkins 1983). Taurine in-

sufficiency is associated with impaired bile acid secretion, reduced

absorption or fat and fat-soluble vitamins (particularly vitamin

D), abnormal hepatic function, and hepatic cholestasis associated

with prolonged administration of parenteral nutrition in preterm

infants (Sturman 1995; Howard 1992; Spencer 2005).

Taurine is abundant in human milk, but it is present in much lower

concentrations in cow milk and is removed in the processing of

infant formulae (Rassin 1978; Agostini 2000). Preterm infants fed

formula low in taurine have lower plasma taurine levels than those

fed human milk (Gaull 1977). Given the potential for taurine de-

ficiency to affect growth and development, consensus statements

have recommended that formula milk fed preterm infants receive

about 4.5 to 9.0 milligrams per kilogram of taurine per day (Tsang

1993). Formula milks for preterm infants are supplemented with

taurine to the same levels as found in human milk- about 3 to

8 milligrams per 100 millilitres (AAP 1998; Klein 2002). Sim-

ilarly, observational studies have demonstrated that preterm in-

fants who receive parenteral nutrition without supplemental tau-

rine have depleted taurine body pools during the first weeks af-

ter birth (Zelikovic 1990). Modern amino acid solutions for par-

enteral nutrition contain levels of taurine that are more than suf-

ficient to meet recommended needs (see: www.ashp.org/ahts).

O B J E C T I V E S

To evaluate the effect of taurine supplementation for preterm or

low birth weight infants on growth and development. The effects

of enteral and parenteral taurine supplementation were evaluated

in separate comparisons.

The following subgroup analyses were planned:

1. Trials where participants were predominantly (more than 80%)

very low birth weight (less than 1500 grams) or very preterm (born

before 32 weeks gestation) infants.

2. Trials where the aim was to give more than 9 milligrams per

kilogram per day of taurine (more than the enteral intake recom-

mended by Tsang 1993 ).

M E T H O D S

Criteria for considering studies for this review

Types of studies

Controlled trials using either random or quasi-random patient

allocation.

Types of participants

Preterm (born before 37 weeks gestation) or low birth weight (less

than 2500 grams) infants.

Types of interventions

Taurine supplementation versus no supplementation or placebo,

by the parenteral or enteral route. Starting age should be within

28 days of birth. Trials should have aimed to provide at least 4.5

milligrams per kilogram of taurine per day for at least one week

to infants in the intervention group. Infants in the control groups

should have received less than 4.5 milligrams per kilogram of tau-

rine per day. Studies in which there were co-interventions, for ex-

ample supplementation with other nutrients as well as taurine in

the intervention group versus no supplementation in the control

group, were excluded.

Types of outcome measures

Primary:

1. Growth:

(a) Rates of weight gain (grams per day, or grams per kilogram

per day), linear growth (millimetres per week), head growth (mil-

limetres per week), or skinfold thickness growth (millimetres per

week) during the trial period.

(b) Long-term growth: weight, height, or head circumference

(and/or proportion of infants who remain below the tenth per-

centile for the index population’s distribution) assessed at inter-

vals from six months of age (corrected for preterm birth), to 18

months, and beyond.

2. Development:

(a) Neurodevelopmental outcomes at greater than or equal to 12

months of age (corrected for preterm birth) measured using vali-

dated assessment tools.

(b) Severe neurodevelopmental disability defined as any one or

combination of the following: non-ambulant cerebral palsy, devel-

opmental delay (developmental quotient less than 70), auditory

and visual impairment.

(c) Cognitive and educational outcomes at aged more than five

years old: Intelligence quotient and/or indices of educational



achievement measured using a validated assessment tool (includ-

ing school examination results).

Secondary:

3. Physiological measures of intestinal fat absorption such as the

percentage of fat absorption or of faecal fat excretion.

4. Biochemical measures of hepatic function: plasma bilirubin lev-

els and levels of hepatic enzymes (for example, alanine aminotrans-

ferase, gamma-glutamyltranspeptidase).

5. Electrophysiological measures of retinal function or visual acuity

(for example, electroretinography or visual evoked potentials) and

longer term assessments of visual acuity.

6. Electrophysiological measures of auditory function such as au-

ditory brainstem responses and transient evoked otoacoustic emis-

sions and longer term assessments of auditory acuity.

7. Death in the neonatal period (up to 28 days) and death prior

to hospital discharge.

8. Neonatal morbidity:

(a) intracranial haemorrhage; all grades (grades I-IV), and severe

haemorrhage- grade III (ventricles distended with blood) or IV

(parenchymal involvement) (Papile 1978).

(b) cystic periventricular leucomalacia defined as cysts detected in

the periventricular area on ultrasound, computerised tomography

or magnetic resonance imaging.

(c) retinopathy of prematurity; all stages, and of stage 3 or more

based on international classification (ICROP 1984).

(d) chronic lung disease defined as requirement for supplemental

oxygen requirement at 36 weeks postmenstrual age.

(e) necrotising enterocolitis defined using Bell’s criteria (or modi-

fications), that is, the presence of at least two of the following fea-

tures: pneumatosis coli on abdominal radiograph; abdominal dis-

tension or abdominal radiograph with gaseous distension or frothy

appearance of bowel lumen (or both); blood in stool; lethargy,

hypotonia, or apnea, or combination of these (Bell 1978).

Search methods for identification of studies

The standard search strategy of the Cochrane Neonatal Re-

view Group was used. This strategy consisted of searches of the

Cochrane Central Register of Controlled Trials (CENTRAL, The

Cochrane Library, Issue 2, 2007), MEDLINE (1966 - June 2007),

and EMBASE (1980 - June 2007) using the following text words

and MeSH terms: Infant, Newborn OR infan* OR neonat* OR

low birth weight OR LBW OR prematur* OR preterm AND tau-

rine OR cysteine OR methionine OR sulfur amino acid OR sul-

phur amino acid. The search outputs were limited with the rel-

evant search filters for clinical trials. No language restriction was

applied.

References in previous reviews and included studies were exam-

ined. Abstracts presented at the Society for Pediatric Research

and European Society for Pediatric Research between 1980 and

2006/7 were searched by hand. Trials reported only as abstracts

were eligible if sufficient information was available from the report

or from contact with the authors to fulfil the inclusion criteria.

The Journal of Pediatric Gastroenterology and Nutrition (1980 -

2005) was searched by hand. The UK National Research Regis-

ter (http://www.nrr.nhs.uk) and Current Controlled Trials (http:/

/www.controlled-trials.com) websites were searched for completed

or ongoing trials (MeSH terms: taurine, infants, newborn, nutri-

tion).

Data collection and analysis

1. Two review authors screened the title and abstract of all of the

studies identified by the above search strategy and the full text

of the report of each study identified as of potential relevance.

These independent assessments followed pre-specified guidelines

for inclusion. The decision to include or exclude a specific study

was made by consensus of all of the review authors.

2. The criteria and standard methods of the Cochrane Neonatal

Review Group were used to assess the methodological quality of

the included trials. Trial quality in terms of allocation concealment,

blinding of parents or caregivers and assessors to intervention,

and completeness of assessment in all randomised individuals was

evaluated.

3. A data collection form to aid extraction of relevant information

and data from each included study was used. Two review authors

extracted the data separately. These data were compared and dif-

ferences were resolved by consensus.

4. The standard method of the Cochrane Neonatal Review Group

was used to analyse and synthesize the data. The fixed effect model

was used for meta-analysis. The effects were expressed as relative

risk and 95% confidence interval and risk difference and 95%

confidence interval for categorical data.

5. Heterogeneity between trial results was examined by inspecting

the forest plots and quantifying the impact of heterogeneity in any

meta-analysis using a measure of the degree of inconsistency in

the studies’ results (I2- squared statistic). If statistical heterogene-

ity was detected, the review authors explored the possible causes

(for example, differences in study quality, participants, interven-

tion regimens, or outcome assessments) using post hoc subgroup

analyses.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies.

Nine trials fulfilled the review inclusion criteria (Bellentani 1988;

Bijleveld 1987; Cooke 1984; Galeano 1987; Jarvenpaa 1983;

Michalk 1988; Okamoto 1984; Tyson 1989; Zamboni 1993).



These are described in detail in the table, Characteristics of

included studies. Two studies were excluded (Harding 1989;

Wasserhess 1993; see table, Characteristics of excluded studies).

All of the included studies were undertaken during the late 1970s

and 1980s by investigators attached to neonatal units in Europe

and North America. In total, 189 infants participated. The par-

ticipants in eight of the trials were clinically stable preterm or low

birth weight infants who were fully enterally fed. The infants re-

ceived taurine in formula milk at a concentration of between about

3 to 6 milligrams per 100 millilitres. Control infants received the

same formula without added taurine. The intervention was con-

tinued for between three weeks and four months. One trial com-

pared taurine supplementation (10.8 milligrams/kilogram/day)

administered with parenteral nutrition for 10 days (Cooke 1984).

Most trials assessed only short-term outcomes, principally growth

parameters (usually weight) during the study period, changes in

plasma levels of taurine, biochemical measures of hepatic function

and nitrogen balance, and intestinal fat absorption. One trial as-

sessed visual and auditory evoked potentials, and reported neona-

tal mortality and morbidities (Tyson 1989). None of the trials as-

sessed any long-term outcomes.

Risk of bias in included studies

Methodological quality was generally poor. Only one trial at-

tempted to maintain allocation concealment and to blind carers

and assessors to the intervention (Tyson 1989). Follow-up was

complete or near complete in most of the studies.

Effects of interventions

ENTERAL TAURINE SUPPLEMENTATION VERSUS NO

SUPPLEMENTATION

Growth (Outcome 01.01.01- 01.01.06):

Four trials reported growth data within the neonatal period

(Bellentani 1988; Jarvenpaa 1983; Okamoto 1984; Tyson 1989).

None reported any statistically significant differences in weight

gain. Numerical data were not available for Okamoto 1984. Meta-

analysis of data from the other three trials did not detect a statisti-

cally significant difference: weighted mean difference -0.64 (95%

confidence interval -1.84, 0.56) grams/kilogram/day. Okamoto

1984 and Tyson 1989 reported the change in length and head

circumference during the neonatal period. Neither found any sta-

tistically significant differences (Okamoto 1984 did not provide

any numerical data).

Four trials reported growth rates from the point of regained birth

weight until three to four months chronological age (Galeano

1987; Jarvenpaa 1983; Michalk 1988; Zamboni 1993). None of

the individual trials, nor meta-analyses of the data, found a statis-

tically significant difference in the rate of weight gain [weighted

mean difference -0.25 (95% confidence interval -1.16, 0.66)

grams/kilogram/day], change in length [weighted mean difference

0.37 (95% confidence interval -0.23, 0.98) millimetres/week], or

change in head circumference [weighted mean difference 0.15

(95% confidence interval -0.19, 0.50) millimeters/week]. None

of the trials reported any long-term growth outcomes.

Development: Not reported by any of the included trials.

Intestinal fat absorption (Outcome 01.02): Four trials reported

intestinal fat absorption (percentage of total intake). Three tri-

als reported no statistically significant difference (Bijleveld 1987;

Jarvenpaa 1983; Okamoto 1984). Okamoto 1984 did not re-

port standard deviations or data to allow their calculation. One

trial found statistically higher fat absorption in the taurine-sup-

plemented group (Galeano 1987). Meta-analysis of data from

Bijleveld 1987, Galeano 1987, and Jarvenpaa 1983 demonstrated

a statistically infant higher level of fat absorption: weighted mean

difference 4.0 (95% confidence interval 1.4, 6.6) percent of in-

take.

Biochemical measures of hepatic function: Not reported by any

of the included trials.

Electrophysiological measures of retinal function (Outcome

01.03): Tyson 1989 did not detect any statistically significant

differences in latency or amplitude on electroretinography.

Electrophysiological measures of auditory function (Outcome

01.04): Tyson 1989 reported wave latency for auditory brainstem-

evoked responses for three waves (I, III, and V), each at two fre-

quencies (20/second, and 67/second). Of these six comparisons,

only one (wave I, 67/second) was statistically significantly differ-

ent: mean difference -0.5 (-0.93, -0.07) milliseconds.

Death in the neonatal period (Outcome 01.05): Tyson 1989

reported no statistically significant difference (no deaths in the

treatment group vs. one death in the control group).

Neonatal morbidity (Outcome 01.06): Tyson 1989 reported no

statistically significant difference in the incidence of necrotising

enterocolitis (three cases in the treatment group vs. one in the

control group). No other neonatal morbidities were reported by

any of the trials.

PARENTERALTAURINE SUPPLEMENTATION VERSUS

NO SUPPLEMENTATION

Cooke 1984 did not detect any statistically significant difference

in the plasma levels of conjugated bilirubin, alanine aminotrans-

ferase, or gamma-glutamyltranspeptidase measured at three, five,

and nine days after trial commencement. Standard deviations (or

any data to allow their imputation) were not reported. Cooke 1984

did not report any other outcomes.



Subgroup analyses

1. Birth weight: Only Tyson 1989 recruited participants who were

predominantly very low birth weight or very preterm (see above

for details).

2. Dose: Cooke 1984 prescribed parenteral taurine at a dose of

10.8 milligrams/kilogram/day. All of the enteral supplementation

trials prescribed taurine at doses less than 9 milligrams/kilogram/

day (see above for details).

D I S C U S S I O N

The available data from randomised controlled trials do not pro-

vide any evidence that taurine supplementation of formula milk

or parenteral nutrition has important clinical effects on growth

and development in preterm or low birth weight infants. How-

ever, most participants in the identified trials were clinically stable

infants of gestational age at birth greater than 30 weeks. None of

the trials found that plasma taurine levels were affected by taurine

supplementation. It may be that dietary taurine is not essential to

maintain tissue levels for this population. Taurine may only be an

essential dietary requirement in very preterm or critically ill in-

fants where metabolic pathways for renal reabsorption and hepatic

biosynthesis are insufficient to maintain tissue levels. The trial that

recruited infants likely to fall into this category was underpowered

(N = 47) to detect important effects on growth, development, or

neonatal mortality and morbidity (Tyson 1989).

All of the included trials were undertaken before addition of tau-

rine to formula milk and parenteral nutrition solutions became

standard practice in the mid-to-late 1980s. The introduction of

this practice was prompted by reports of electroretinographic ab-

normalities associated with taurine deficiency in animal models

and in children receiving prolonged parenteral nutrition without

taurine (Hayes 1975; Geggel 1985; Ament 1986). The only trial in

preterm infants that undertook electroretinographic assessments

did not find any evidence of an effect of taurine supplementation

(Tyson 1989). Taurine deficiency has also been associated with

delayed auditory brainstem-evoked response maturation in ani-

mal models (Vallecalle 1991). Although Tyson 1989 reported that

taurine supplementation resulted in a reduction in wave latency

for auditory brainstem-evoked responses in one (of six) wave/fre-

quency comparisons, the clinical importance of this finding is un-

certain. In contrast, taurine supplementation in term infants has

been associated with prolongation of auditory brainstem-evoked

response wave latencies suggesting that taurine may delay auditory

maturation (Dhillon 1998). Furthermore, evidence exists that tau-

rine may exacerbate aminoglycoside ototoxicity, a potential adverse

effect that is particularly relevant for very preterm infants where

aminoglycosides are commonly prescribed during the neonatal pe-

riod (Kay 1990).

Only one trial assessed the effect of parenteral taurine supplemen-

tation (Cooke 1984). This small study found no evidence that

taurine affected biochemical indices of hepatic function. However,

since the participating infants were clinically stable, and the dura-

tion of the trial was only ten days, it is not possible to determine

whether parenteral taurine has an important effect on neonatal

cholestasis. It may be worthwhile undertaking further studies to

determine whether different doses and duration of taurine supple-

mentation are effective in preventing or treating parenteral-nutri-

tion associated cholestasis in very preterm or critically ill infants.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

Despite that lack of data from randomised controlled trials, it is

likely that taurine will continue to be added to formula milks

and parenteral nutrition solutions used for feeding preterm and

low birth weight infants. Current practice aims to provide taurine

supplementation at similar input levels to those on human breast

milk as it is assumed that supplementation to this level is not

harmful.

Implications for research

Given the putative association of taurine deficiency with various

adverse outcomes, further randomised controlled trials of taurine

supplementation versus no supplementation in preterm or low

birth weight infants are unlikely to be viewed as a research priority

(Heird 2004). There may be clinical questions relating to dose

and duration of taurine supplementation in specific subgroups of

preterm infants that should be addressed in future studies.

A C K N O W L E D G E M E N T S

Don Corleone for translating Bellentani 1988.



R E F E R E N C E S

References to studies included in this review

Bellentani 1988 {published data only}

Bellentani S, Rocchi E, Casalgrandi G, Pecorari M, Farina

F, Cappella L. Effect of enteral taurine supplementation

on nutritional indices and hepatic function in preterm

infants [Effetto della supplementazione di taurina

nell’alimentazione del neonato prematuro su alcuni indici

bioumorali di funzionalita’ epatica]. Pediatrica oggi 1988;8:

402–7.

Bijleveld 1987 {published data only}

Bijleveld CM, Vonk RJ, Okken A, Fernandes J. Fat

absorption in preterm infants fed a taurine-enriched

formula. European Journal of Paediatics 1987;146:128–30.

Cooke 1984 {published data only}

Cooke RJ, Whitington PF, Kelts D. Effect of taurine

supplementation on hepatic function during short-term

parenteral nutrition in the premature infant. Journal of

Pediatric Gastroenterology and Nutrition 1984;3:234–8.

Galeano 1987 {published data only}

Galeano NF, Darling P, Lepage G, Leroy C, Collet S,

Giguere R, Roy CC. Taurine supplementation of a

premature formula improves fat absorption in preterm

infants. Pediatric Research 1987;22:67–71.

Jarvenpaa 1983 {published data only}

Jarvenpaa AL. Feeding the low-birth-weight infant. IV. Fat

absorption as a function of diet and duodenal bile acids.

Paediatrics 1983;72:684–9.∗ Jarvenpaa AL, Raiha NC, Rassin DK, Gaull GE. Feeding

the low-birth-weight infant: I. Taurine and cholesterol

supplementation of formula does not affect growth and

metabolism. Pediatrics 1983;71:171–8.

Jarvenpaa AL, Rassin DK, Kuitunen P, Gaull GE, Raiha NC.

Feeding the low-birth-weight infant. III. Diet influences

bile acid metabolism. Paediatrics 1983;72:677–83.

Rassin DK, Gaull GE, Jarvenpaa AL, Raiha NC. Feeding

the low-birth-weight infant: II. Effects of taurine and

cholesterol supplementation on amino acids and cholesterol.

Pediatrics 1983;71:179–86.

Watkins JB, Jarvenpaa AL, Szczepanik-Van Leeuwen P,

Klein PD, Rassin DK, Gaull G, Raiha NC. Feeding the

low-birth weight infant: V. Effects of taurine, cholesterol,

and human milk on bile acid kinetics. Gastroenterology

1983;85:793–800.

Michalk 1988 {published data only}

Michalk DV, Ringeisen R, Tittor F, Lauffer H, Deeg KH,

Bohles HJ. Development of the nervous and cardiovascular

systems in low-birth-weight infants fed a taurine-

supplemented formula. European Journal of Paediatrics

1988;147:296–9.

Okamoto 1984 {published data only}

Okamoto E, Rassin DK, Zucker CL, Salen GS, Heird WC.

Role of taurine in feeding the low-birth-weight infant.

Journal of Pediatrics 1984;104:36–40.

Tyson 1989 {published data only}

Tyson JE, Lasky R, Flood D, Mize C, Picone T, Paule CL.

Randomized trial of taurine supplementation for infants

less than or equal to 1,300-gram birth weight: effect on

auditory brainstem-evoked responses. Pediatrics 1989;83:

406–15.

Zamboni 1993 {published data only}

Zamboni G, Piemonte G, Bolner A, Antoniazzi F,

Dall’Agnola A, Messner H, Gambaro G, Tato L. Influence

of dietary taurine on vitamin D absorption. Acta Paediatrica

1993;82:811–5.

References to studies excluded from this review

Harding 1989 {published data only}

Harding GF, Grose J, Wilton AY, Bissenden JG. The

pattern reversal VEP in short-gestation infants on taurine

or taurine-free diet. Documenta Ophthalmologica 1989;73:

103–9.

Wasserhess 1993 {published data only}

Wasserhess P, Becker M, Staab D. Effect of taurine on

synthesis of neutral and acidic sterols and fat absorption in

preterm and full-term infants. American Journal of Clinical

Nutrition 1993;58:349–53.

Additional references

AAP 1998

American Academy of Pediatrics (AAP). Committee on

Nutrition. Soy protein-based formulas: recommendations

for use in infant feeding. Pediatrics 1998;101:148–53.

Agostini 2000

Agostoni C, Carratu B, Boniglia C, Riva E, Sanzini E.

Free amino acid content in standard infant formulas:

comparison with human milk. Journal of the American

College of Nutrition 2000;19:434–8.

Ament 1986

Ament ME, Geggel HS, Heckenlively JR, Martin DA,

Kopple J. Taurine supplementation in infants receiving

long-term total parenteral nutrition. Journal of the American

College of Nutrition 1986;5:127–35.

Bell 1978

Bell MJ, Ternberg JL, Feigin RD, et al.Neonatal necrotizing

enterocolitis. Therapeutic decisions based upon clinical

staging. Annals of Surgery 1978;187:1–7.

Chesney 1998a

Chesney RW, Helms RA, Christensen M, Budreau AM,

Han X, Sturman JA. An updated view of the value of

taurine in infant nutrition. Advances in Pediatrics 1998;40:

179–200.

Chesney 1998b

Chesney RW, Helms RA, Christensen M, Budreau AM,

Han X, Sturman JA. The role of taurine in infant nutrition.

Advances in Experimental Medicine and Biology 1998;442:

463–76.



Dhillon 1998

Dhillon SK, Davies WE, Hopkins PC, Rose SJ. Effects of

dietary taurine on auditory function in full-term infants.

Advances in Experimental Medicine and Biology 1998;442:

507–14.

Gaull 1977

Gaull GE, Rassin DK, Raiha NC, Heinonen K. Milk

protein quantity and quality in low-birthweight infants. III.

Effects on sulfur amino acids in plasma and urine. Journal

of Pediatrics 1977;90:348–55.

Geggel 1985

Geggel HS, Ament ME, Heckenlively JR, Martin DA,

Kopple JD. Nutritional requirement for taurine in patients

receiving long-term parenteral nutrition. New England

Journal of Medicine 1985;312:142–6.

Hayes 1975

Hayes KC, Carey RE. Retinal degeneration associated with

taurine deficiency in the cat. Science 1975;188:949-51.

Heird 2004

Heird WC. Taurine in neonatal nutrition--revisited.

Archives of Disease in Childhood 2004;89:F473–4.

Horner 1997

Horner KC, Aurousseau C. Immunoreactivity for taurine

in the cochlea: its abundance in supporting cells. Hearing

Research 1997;109:135–42.

Howard 1992

Howard D, Thompson DF. Taurine: an essential amino

acid to prevent cholestasis in neonates. Annals of

Pharmacotherapy 1992;26:1390–2.

ICROP 1984

ICROP. An International Classification of Retinopathy of

Prematurity. Pediatrics 1984;74:127–133.

Imaki 1993

Imaki H, Jacobson SG, Kemp CM, Knighton RW,

Neuringer M, Sturman J. Retinal morphology and visual

pigment levels in 6- and 12-month-old rhesus monkeys fed

a taurine-free human infant formula. Journal of Neuroscience

Research 1993;36:290–304.

Kay 1990

Kay IS, Davies WE. The effect of taurine supplementation

on the ototoxicity of neomycin in guinea pigs. European

Archives of Otorhinolaryngology 1990;247:37–9.

Klein 2002

Klein CJ. Nutrient requirements for preterm infant

formulas. Journal of Nutrition 2002;132:1395S-577S.

Massieu 2004

Massieu L, Montiel T, Robles G, Quesada O. Brain amino

acids during hyponatremia in vivo: clinical observations

and experimental studies. Neurochemical Research 2004;29:

73–81.

Papile 1978

Papile LA, Burstein J, Burstein R, Koffler H. Incidence

and evolution of subependymal and intraventricular

hemorrhage: a study of infants with birthweights less than

1,500 grams. Journal of Pediatrics 1978;92:529–34.

Rassin 1978

Rassin DK, Sturman JA, Guall GE. Taurine and other free

amino acids in milk of man and other mammals. Early

Human Development 1978;2:1–13.

Spencer 2005

Spencer AU, Yu S, Tracy TF, et al.Parenteral nutrition-

associated cholestasis in neonates: multivariate analysis

of the potential protective effect of taurine. Journal of

Parenteral and Enteral Nutrition 2005;29:337–43.

Sturman 1980

Sturman J A, Hayes KC. The biology of taurine in nutrition

and development. Advances in Nutritional Research 1980;3:

231–299.

Sturman 1995

Sturman JA, Chesney RW. Taurine in pediatric nutrition.

Pediatric Clinics of North America 1995;42:879–97.

Thibeault 2000

Thibeault DW. The precarious antioxidant defenses of the

preterm infant. American Journal of Perinatology 2000;17:

167–81.

Trachtman 1988

Trachtman H, Barbour R, Sturman JA, Finberg L. Taurine

and osmoregulation: taurine is a cerebral osmoprotective

molecule in chronic hypernatremic dehydration. Pediatric

Research 1988;23:35–9.

Trachtman 1990

Trachtman H, del Pizzo R, Sturman JA. Taurine and

osmoregulation. III. Taurine deficiency protects against

cerebral edema during acute hyponatremia. Pediatric

Research 1990;27:85–8.

Tsang 1993

Tsang RC, Lucas A, Uauy R, Zlotkin S, eds. Nutritional

Needs of the Preterm Infant: Scientific Basis and Practical

Guidlines. New York: Caduceus Medical Publishers, 1993.

Vallecalle 1991

Vallecalle Sandoval MH, Heaney G, Sersen E, Sturman JA.

Comparison of the developmental changes of the brainstem

auditory evoked response (BAER) in taurine-supplemented

and taurine-deficient kittens. International Journal of

Developmental Neuroscience 1991;9:571–9.

Watkins 1983

Watkins JB, Jarvenpaa AL, Szczepanik-Van Leeuwen P,

et al.Feeding the low-birth weight infant: V. Effects of

taurine, cholesterol, and human milk on bile acid kinetics.

Gastroenterology 1983;85:793–800.

Wharton 2004

Wharton BA, Morley R, Isaacs EB, Cole TJ, Lucas A. Low

plasma taurine and later neurodevelopment. Archives of

Disease in Childhood 2004;89:F473–4.

Zelikovic 1990

Zelikovic I, Chesney RW, Friedman AL, Ahlfors CE.

Taurine depletion in very low birth weight infants



receiving prolonged total parenteral nutrition: role of renal

immaturity. Journal of Pediatrics 1990;116:301–6.∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Bellentani 1988

Methods Blinding of randomisation: can’t tell

Blinding of intervention: no

Complete follow-up: yes

Blinding of outcome measurement: can’t tell

Participants 16 clinically stable low birth weight infants (gestational age 32 to 37 weeks). Infants were excluded if there

was evidence of jaundice

Interventions Treatment (N=8): Cow milk formula (Similac) with taurine added to a concentration of 45 milligrams/

litre.

Control (N=8): Same formula without added taurine.

Intervention assigned for 20 days.

Outcomes Growth (weight gain) during the 20 days trial period, and biochemical measures of hepatic function

Notes Setting: Instituto di Semeiotica Medica, Modena, Italia.

Risk of bias

Item Authors’ judgement Description

Allocation concealment? Unclear B - Unclear

Bijleveld 1987


Blinding of intervention: yes


Blinding of outcome measurement: can’t tell

Participants 9 fully enterally fed preterm infants (gestational age at birth 28-32 weeks)

Interventions Treatment (N=5): Cow milk formula (Almiron AB) with added taurine ( 46 milligrams/litre ).


Infants enrolled during third week after birth then fed study formula for 4 weeks

Outcomes Fat absorption.

Notes Setting: University Hospital Groningen, The Netherlands.

Further data courtesy of Dr Bijleveld.

Risk of bias



Bijleveld 1987 (Continued)



Cooke 1984




Blinding of outcome measurement: no

Participants 20 infants of 34 weeks gestation or less, appropriate for gestational age. Infants were excluded if there was

evidence of hepatobiliary dysfunction

Interventions Treatment (N=10): Parenteral nutrition and taurine to give daily concentration of 10.8 milligrams/kilo-

gram/day.

Control (N=10): Parenteral nutrition without added taurine.

Outcomes Hepatic function, plasma taurine levels.

Notes Setting: University of Tennessee, USA.

Risk of bias



Galeano 1987





Participants Preterm infants appropriate for gestational age, excluded if major congenital abnormality, haemolytic

disease, hyaline membrane disease or notable respiratory distress

Interventions Treatment (N=8): Nutrient-enriched (“preterm”) cow milk formula with taurine at a concentration of 50

milligrams/litre.


Participants were randomised within the first 48 hours of birth. The milk used was introduced at the

commencement of feeds and continued exclusively until 3 months of age

Outcomes Urinary taurine excretion, energy balance, nitrogen balance, fat absorption.

Growth during the trial period.



Galeano 1987 (Continued)

Notes Setting: Hopital Ste-Justine and le Centre Hospitalier, Quebec, Canada

Risk of bias



Jarvenpaa 1983



Complete follow-up: no


Participants 31 infants of between 31 and 36 weeks gestation, birth weight of 2200g or less (appropriate for gestational

age).

Setting: Children’s Hospital, Helsinki, Finland (late 1970s)

Interventions Treatment (N=17): Standard (“term”) cow milk formula with 38 milligrams/litre of taurine.

Control (N=14): Cow milk formula without added taurine.

Outcomes Growth, nitrogen balance,bile acid kinetics, fat absorption (35% loss-to-follow up for intervention group

at 4 months assessment)

Notes NB. The length and head circumference growth rates data were reported as “per metre at birth”. We

corrected for this by assuming an average length at birth of 44cm, and average head circumference at birth

of 32cm

Risk of bias



Michalk 1988





Participants 20 low birth weight infants.

Interventions Treatment (N=10): Cow milk formula with taurine at 60 milligrams/litre.

Control (N=10): Cow milk formula without added taurine.

Intervention assigned for 16 weeks.



Michalk 1988 (Continued)

Outcomes Growth, nitrogen balance, plasma taurine levels.

Notes Setting: Universitats-Kinderklinik, Erlangen, Germany.

Risk of bias



Okamoto 1984





Participants 10 infants of birth weight less than 1700 grams, gestational age at birth less than 34 weeks, appropriate

for gestational age

Interventions Treatment (N=5): Cow milk formula with taurine at concentration of about 30 milligrams/litre.

Control: (N=5): Same formula without added taurine.

Intervention continued until infants reached a weight of 2100 grams

Outcomes Growth, plasma taurine concentration, bile salt concentrations, fat absorption

Notes Setting: Veterans Administration Hospital, and Columbia University, New York, USA

Risk of bias



Tyson 1989

Methods Blinding of randomisation: yes

Blinding of intervention: yes


Blinding of outcome measurement: yes

Participants 47 preterm infants of birth weight less than 1300 grams were enrolled at between 7 and 10 days after birth.

Infants receiving (or likely to receive) any human milk were ineligible. Other exclusion criteria: maternal

drug misuse, major congenital anomalies, intracerebral or intraventricular haemorrhage, persisting need

for ventilatory support, enteral feed intolerance, frequent apnoeas, patent ductus arteriosus



Tyson 1989 (Continued)

Interventions Treatment (N=23): Adapted cow milk formula supplemented with taurine (45 milligrams/litre).

Control (N=24): Same milk without taurine supplementation (taurine concentration less than 5 milligrams

per litre).

Allocated formula continued until infants were discharged from hospital, or attained a weight of 2500

grams, or were withdrawn from the study

Outcomes Growth, feed intolerance and necrotising enterocolitis, electroretinography, auditory evoked potentials

Notes Setting: University of Texas Southwestern Medical Centre, USA

Risk of bias


Allocation concealment? Yes A - Adequate

Zamboni 1993





Participants 30 preterm infants, appropriately grown for gestation, healthy and free from problems that would interfere

with feeding or limit milk intake

Interventions Treatment (N=19): Adapted cow milk formula supplemented with taurine (65 milligrams/litre).

Control (N=11): Same formula without taurine.

Infants were fed milk from commencement of feeds until 3 months of age

Outcomes Growth parameters during trial period. Plasma taurine, bile acids, and vitamin D levels

Notes Setting: University of Verona, Italy.

Risk of bias





Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Harding 1989 Harding 1989 assessed the effect of enteral taurine supplementation on visual evoked potentials of preterm infants

in a randomised controlled trial. However, the allocation code was not yet broken in the only published report of

this trial to date. We have not been able to obtain further data from the trialists

Wasserhess 1993 Wasserhess 1993 reported a randomised crossover study of taurine supplementation in preterm infants. The

intervention period was less than one week



D A T A A N D A N A L Y S E S

Comparison 1. Enteral taurine supplementation versus no supplementation

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Growth during trial period 6 Mean Difference (IV, Fixed, 95% CI) Subtotals only

1.1 Weight gain

during neonatal period

(grams/kilogram/day)

3 81 Mean Difference (IV, Fixed, 95% CI) -0.64 [-1.84, 0.56]

1.2 Weight gain until

three/four months

(grams/kilogram/day)


1.3 Length change

during neonatal period

(millimetres/week)


1.4 Length change

over three/four months

(millimetres/week)

4 80 Mean Difference (IV, Fixed, 95% CI) 0.37 [-0.23, 0.98]

1.5 Head circumference

change during neonatal period

(millimetres/week)

1 37 Mean Difference (IV, Fixed, 95% CI) Not estimable

1.6 Head circumference

change over three/four months

(millimetres/week)


2 Intestinal fat absorption

(percentage of total intake)

4 42 Mean Difference (IV, Fixed, 95% CI) 4.00 [1.43, 6.58]

3 Electroretinography 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only

3.1 Cornea negative potential-

latency (milliseconds)


3.2 Cornea negative potential-

amplitude (microVolts)


3.3 Cornea positive potential-

latency (milliseconds)


3.4 Cornea positive potential-

amplitude (microVolts)


4 Auditory brainstem-evoked

responses

1 Mean Difference (IV, Fixed, 95% CI) Subtotals only

4.1 Wave I latency

(milliseconds): 20/second


4.2 Wave I latency


1 32 Mean Difference (IV, Fixed, 95% CI) -0.5 [-0.93, -0.07]

4.3 Wave III latency



4.4 Wave III latency



4.5 Wave V latency





4.6 Wave V latency



5 Neonatal mortality 1 47 Risk Ratio (M-H, Fixed, 95% CI) 0.35 [0.01, 8.11]

6 Incidence of necrotising

enterocolitis

1 47 Risk Ratio (M-H, Fixed, 95% CI) 3.13 [0.35, 27.96]

Analysis 1.1. Comparison 1 Enteral taurine supplementation versus no supplementation, Outcome 1

Growth during trial period.

Review: Effect of taurine supplementation on growth and development in preterm or low birth weight infants

Comparison: 1 Enteral taurine supplementation versus no supplementation

Outcome: 1 Growth during trial period

Study or subgroup Taurine ControlMean

Difference WeightMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

1 Weight gain during neonatal period (grams/kilogram/day)

Bellentani 1988 8 14.8 (3.3) 8 16.1 (1.5) 22.9 % -1.30 [ -3.81, 1.21 ]

Jarvenpaa 1983 14 12.8 (3) 14 13.6 (1.8) 43.0 % -0.80 [ -2.63, 1.03 ]

Tyson 1989 19 18 (2) 18 18 (4) 34.2 % 0.0 [ -2.06, 2.06 ]

Subtotal (95% CI) 41 40 100.0 % -0.64 [ -1.84, 0.56 ]

Heterogeneity: Chi2 = 0.67, df = 2 (P = 0.72); I2 =0.0%

Test for overall effect: Z = 1.05 (P = 0.30)

2 Weight gain until three/four months (grams/kilogram/day)

Galeano 1987 8 22.9 (5.9) 7 26.4 (5.8) 2.3 % -3.50 [ -9.43, 2.43 ]

Jarvenpaa 1983 11 19.6 (3.5) 13 20.6 (4.9) 7.2 % -1.00 [ -4.37, 2.37 ]

Michalk 1988 10 13.7 (2.2) 10 14.1 (2) 24.2 % -0.40 [ -2.24, 1.44 ]

Zamboni 1993 10 14.1 (1.2) 11 14.1 (1.4) 66.3 % 0.0 [ -1.11, 1.11 ]

Subtotal (95% CI) 39 41 100.0 % -0.25 [ -1.16, 0.66 ]



3 Length change during neonatal period (millimetres/week)

Tyson 1989 19 10 (3) 18 11 (3) 100.0 % -1.00 [ -2.93, 0.93 ]

Subtotal (95% CI) 19 18 100.0 % -1.00 [ -2.93, 0.93 ]

Heterogeneity: not applicable


4 Length change over three/four months (millimetres/week)

Galeano 1987 8 8 (2.8) 7 10 (2.6) 4.9 % -2.00 [ -4.73, 0.73 ]

Jarvenpaa 1983 11 8.1 (1.5) 13 8.8 (1.3) 28.3 % -0.70 [ -1.83, 0.43 ]

-10 -5 0 5 10

Favours control Favours taurine

(Continued . . . )



(. . . Continued)



Difference


Michalk 1988 10 8.3 (2) 10 7.3 (1.2) 17.4 % 1.00 [ -0.45, 2.45 ]

Zamboni 1993 10 10 (1) 11 9 (1) 49.5 % 1.00 [ 0.14, 1.86 ]

Subtotal (95% CI) 39 41 100.0 % 0.37 [ -0.23, 0.98 ]

Heterogeneity: Chi2 = 9.12, df = 3 (P = 0.03); I2 =67%


5 Head circumference change during neonatal period (millimetres/week)

Tyson 1989 19 11 (1) 18 11 (2) 100.0 % 0.0 [ -1.03, 1.03 ]

Subtotal (95% CI) 19 18 100.0 % 0.0 [ -1.03, 1.03 ]



6 Head circumference change over three/four months (millimetres/week)

Galeano 1987 8 9.4 (4.2) 7 8.3 (2.6) 1.0 % 1.10 [ -2.39, 4.59 ]

Jarvenpaa 1983 11 5.7 (1.4) 13 5.8 (1.4) 9.3 % -0.10 [ -1.22, 1.02 ]

Michalk 1988 10 5.2 (0.5) 10 5 (0.5) 61.2 % 0.20 [ -0.24, 0.64 ]

Zamboni 1993 10 5.8 (0.7) 11 5.7 (0.8) 28.5 % 0.10 [ -0.54, 0.74 ]

Subtotal (95% CI) 39 41 100.0 % 0.15 [ -0.19, 0.50 ]



Test for subgroup differences: Chi2 = 4.19, df = 5 (P = 0.52), I2 =0.0%

-10 -5 0 5 10





Intestinal fat absorption (percentage of total intake).



Outcome: 2 Intestinal fat absorption (percentage of total intake)


DifferenceMean

Difference


Bijleveld 1987 5 71 (11) 4 79 (4) -8.00 [ -18.41, 2.41 ]

Galeano 1987 8 92.5 (3.2) 7 87.5 (2.1) 5.00 [ 2.29, 7.71 ]

Jarvenpaa 1983 4 83.6 (4) 4 84 (13) -0.40 [ -13.73, 12.93 ]

Okamoto 1984 5 86.5 (0) 5 86.8 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 22 20 4.00 [ 1.43, 6.58 ]

Heterogeneity: Chi2 = 6.05, df = 2 (P = 0.05); I2 =67%


Test for subgroup differences: Not applicable

-100 -50 0 50 100





Electroretinography.



Outcome: 3 Electroretinography



Difference


1 Cornea negative potential- latency (milliseconds)

Tyson 1989 17 14.8 (2.1) 15 14.4 (1.7) 100.0 % 0.40 [ -0.92, 1.72 ]

Subtotal (95% CI) 17 15 100.0 % 0.40 [ -0.92, 1.72 ]



2 Cornea negative potential- amplitude (microVolts)

Tyson 1989 17 7 (3.7) 15 8.7 (3.6) 100.0 % -1.70 [ -4.23, 0.83 ]

Subtotal (95% CI) 17 15 100.0 % -1.70 [ -4.23, 0.83 ]



3 Cornea positive potential- latency (milliseconds)

Tyson 1989 17 36.6 (3.7) 15 36.8 (3.6) 100.0 % -0.20 [ -2.73, 2.33 ]

Subtotal (95% CI) 17 15 100.0 % -0.20 [ -2.73, 2.33 ]



4 Cornea positive potential- amplitude (microVolts)

Tyson 1989 17 20.6 (8.1) 15 23.7 (9) 100.0 % -3.10 [ -9.06, 2.86 ]

Subtotal (95% CI) 17 15 100.0 % -3.10 [ -9.06, 2.86 ]



Test for subgroup differences: Chi2 = 3.05, df = 3 (P = 0.38), I2 =2%

-10 -5 0 5 10

Favours taurine Favours control




Auditory brainstem-evoked responses.



Outcome: 4 Auditory brainstem-evoked responses



Difference


1 Wave I latency (milliseconds): 20/second

Tyson 1989 17 2.8 (0.5) 15 3 (0.7) 100.0 % -0.20 [ -0.63, 0.23 ]

Subtotal (95% CI) 17 15 100.0 % -0.20 [ -0.63, 0.23 ]



2 Wave I latency (milliseconds): 67/second

Tyson 1989 17 2.9 (0.5) 15 3.4 (0.7) 100.0 % -0.50 [ -0.93, -0.07 ]

Subtotal (95% CI) 17 15 100.0 % -0.50 [ -0.93, -0.07 ]



3 Wave III latency (milliseconds): 20/second

Tyson 1989 17 5.3 (0.4) 15 5.6 (0.5) 100.0 % -0.30 [ -0.62, 0.02 ]

Subtotal (95% CI) 17 15 100.0 % -0.30 [ -0.62, 0.02 ]



4 Wave III latency (milliseconds): 67/second

Tyson 1989 17 5.7 (0.4) 15 5.9 (0.6) 100.0 % -0.20 [ -0.56, 0.16 ]

Subtotal (95% CI) 17 15 100.0 % -0.20 [ -0.56, 0.16 ]



5 Wave V latency (milliseconds): 20/second

Tyson 1989 17 7.7 (0.6) 15 7.9 (0.8) 100.0 % -0.20 [ -0.70, 0.30 ]

Subtotal (95% CI) 17 15 100.0 % -0.20 [ -0.70, 0.30 ]



6 Wave V latency (milliseconds): 67/second

Tyson 1989 17 8.3 (0.5) 15 8.6 (0.7) 100.0 % -0.30 [ -0.73, 0.13 ]

Subtotal (95% CI) 17 15 100.0 % -0.30 [ -0.73, 0.13 ]



Test for subgroup differences: Chi2 = 1.47, df = 5 (P = 0.92), I2 =0.0%

-1 -0.5 0 0.5 1





Neonatal mortality.



Outcome: 5 Neonatal mortality

Study or subgroup Taurine Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Tyson 1989 0/23 1/24 100.0 % 0.35 [ 0.01, 8.11 ]

Total (95% CI) 23 24 100.0 % 0.35 [ 0.01, 8.11 ]

Total events: 0 (Taurine), 1 (Control)



0.01 0.1 1 10 100



Incidence of necrotising enterocolitis.



Outcome: 6 Incidence of necrotising enterocolitis

Study or subgroup Taurine Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Tyson 1989 3/23 1/24 100.0 % 3.13 [ 0.35, 27.96 ]

Total (95% CI) 23 24 100.0 % 3.13 [ 0.35, 27.96 ]

Total events: 3 (Taurine), 1 (Control)



0.01 0.1 1 10 100




W H A T ’ S N E W

Last assessed as up-to-date: 19 July 2007.

Date Event Description

5 October 2010 Amended Contact details updated.

H I S T O R Y

Protocol first published: Issue 3, 2006

Review first published: Issue 4, 2007

Date Event Description

15 September 2008 Amended Converted to new review format.

C O N T R I B U T I O N S O F A U T H O R S

Alison Verner, Stan Craig, and William McGuire developed the protocol jointly. Alison Verner and William McGuire conducted the

electronic and hand searches, screened the title and abstract of all studies identified, independently reviewed the full text of potentially

relevant reports, and extracted the data. All authors completed the final review authors.

D E C L A R A T I O N S O F I N T E R E S T

None.

S O U R C E S O F S U P P O R T

Internal sources

• ANU Medical School, Canberra, Australia.

• Royal Maternity Hospital, Belfast, UK.



External sources

• No sources of support supplied

I N D E X T E R M S

Medical Subject Headings (MeSH)

∗Enteral Nutrition; ∗Infant Formula; Infant, Low Birth Weight [∗ growth & development]; Infant, Newborn; Infant, Premature [∗growth

& development]; Randomized Controlled Trials as Topic; Taurine [∗administration & dosage]

MeSH check words

Humans



Documents

CD 006072