Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation:

• weight on admission (mean ± SD): 3220 ± 1370 g;

• gestational age (mean ± SD): 39.1 ± 4.7 weeks;

• age on admission (mean ± SD): 45.5 ± 9.3 hours;

• TSB on admission (mean ± SD): 316.35 ± 65.32 μmol/L.

No fluid supplementation:

• weight on admission (mean ± SD): 3150 ± 1230 g;

• gestational age (mean ± SD): 38.8 ± 4.5 weeks;

• age on admission (mean ± SD): 47.2 ± 8.6 hours;

• TSB on admission (mean ± SD): 312.93 ± 58.31 μmol/L.

Inclusion criteria: healthy term breastfed infants with severe hyperbilirubinaemia.

Exclusion criteria: "We excluded haemolytic disease (ABO or Rh incompatibility and a positive Coomb's test), G6PD deficiency, direct hyperbilirubinaemia, infection, dehydration, and prolonged jaundice persisting beyond 14 days of life."

Pretreatment: "No major differences between the two groups."

Interventions

IV fluid supplementation:

• "In addition to enteral feeding (milk‐fed), patients received IV fluid supplementation. The amount of extra fluid which was given to the supplemented group was 20% of the maintenance. The daily maintenance fluid level considered 80 mL/kg on day 2, 100 mL/kg on day 3 and 120 mL/kg on day 4, 140 mL/kg on day 5, 150 mL on day 6, 160 mL on day 7 and thereafter. The extra fluids were given as intravenous 10% dextrose in the second day of life, 1/5 normal saline 10% dextrose in day 3 of life and thereafter."

No fluid supplementation:

• breastfed or formula‐fed on‐demand.

Outcomes

Serum bilirubin

• Outcome type: continuous.

Number of infants who required exchange transfusion (criteria not stated)

• Outcome type: dichotomous.

Identification

Sponsorship source: none stated.

Country: Jordan.

Setting: NICU in 2 medical centres.

Comments: study conducted between September 2008 and October 2009.

Author's name: Hazem A Al‐Masri.

Institution: Royal Medical Services.

Email: [email protected].

Address: Department of Pediatrics, Royal Medical Services, Jordan.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Unclear risk

Quote: "Infants were divided randomly into two groups."

Authors did not state methods of sequence generation as they only described in a simple statement that "infants were divided randomly..."

Allocation concealment

Unclear risk

No statements on methods of randomisation or party involved sequence generation and allocation (or both) to enable an assessment of whether the 2 steps were performed independently from each other.

Blinding of participants and personnel
All outcomes

High risk

Not stated if blinding occurred but due to nature of intervention (IV drip) as compared to oral feeding only in control group, it is highly unlikely that the researchers were blinded.

Blinding of outcome assessors
All outcomes

Unclear risk

Not stated if the laboratory staff knew group that participants were allocated to.

Incomplete outcome data
All outcomes

Low risk

Results for all 40 infants in each group analysed and presented in Table 2.

Selective outcome reporting

Low risk

Major outcomes specified in methods, namely serum bilirubin at different time points and number of infants who required exchange transfusion reported in sufficient detail in results.

Selective outcome reporting

Low risk

Major outcomes specified in methods, namely serum bilirubin at different time points and number of infants who required exchange transfusion reported in sufficient detail in results.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation:

• birthweight (mean ± SD): 3147 ± 512 g;

• gestational age (mean ± SD): 39.4 ± 0.9 weeks;

• age on admission (mean ± SD): 5.2 ± 2.0 days;

• spontaneous vestex delivery (no (%)): 20 (74.1%)

• TSB on admission (mean ± SD): 386 ± 60 μmol/L.

Oral fluid supplementation:

• birthweight (mean ± SD): 3003 ± 321 g;

• gestational age (mean ± SD): 39.3 ± 1.0 weeks;

• age on admission (mean ± SD): 6.4 ± 1.8 days;

• spontaneous vestex delivery (no (%)): 20 (74.1%)

• TSB on admission (mean ± SD): 369 ± 72 μmol/L.

Inclusion criteria: healthy term infants (≥ 37 weeks' gestation) admitted to the NICU with TSB level ≥ 300 μmol/L and conjugated serum bilirubin levels ≤ 15% of the TSB.

Exclusion criteria: unwell infants (e.g. septicaemia, feed intolerance, kernicterus), major congenital malformation, conjugated hyperbilirubinaemia > 15% of TSB levels, or prolonged jaundice persisting beyond 14 days of life.

Pretreatment: no significant differences between groups in mean birth weight, mean gestational age, ethnic distribution, gender distribution, places of birth, modes of delivery, and types of feeding. No significant differences in proportion with birth trauma, ABO incompatibility, abnormal blood film, G6PD deficiency, herbal intake for breastfeeding mothers, and clinical dehydration. Mean total indirect serum bilirubin on admission were not significantly different. The infants in the enteral group were significantly older on admission than those in IV group (P = 0.02).

Interventions

IV fluid supplementation:

• standard fluid protocol: all infants received a daily maintenance fluid level of 90 mL/kg on day 2, 120 mL/kg on day 3, and 150 mL/kg from day 4 of life onwards;

• additional fluid: also given an additional 10% of their respective total daily fluid requirement to compensate for fluid loss associated with intensive phototherapy. For infants with dehydration, volume of fluid deficit was replaced over 12 hours, in addition to their maintenance and supplemental fluid;

• methods of administration: formula‐fed infants allocated to IV group given half of their total fluid volume as per protocol via 8 divided formula feeds (3 hourly), while the remaining half of the total fluid was given via IV infusion with 1/5 normal saline and 5% dextrose infusion over 24 hours;

• duration of intervention: all infants received IV fluid infusion for 24 hours, after which they reverted to their usual feeding regimen as before enrolment.

Oral fluid supplementation:

• standard fluid protocol: all infants received daily maintenance fluid level of 90 mL/kg on day 2, 120 mL/kg on day 3, and 150 mL/kg from day 4 of life onwards;

• additional fluid: also given an additional 10% of their respective total daily fluid requirement to compensate for fluid loss associated with intensive phototherapy. For infants with dehydration, volume of fluid deficit was replaced over 12 hours, in addition to their maintenance and supplemental fluid;

• methods of administration: infants kept on their feeding type (breast, formula, or mixed) as before enrolment. Once enrolled, formula‐fed infants were given their total daily fluid volume as per protocol in 8 divided doses (3 hourly). Breastfed infants received half of the total volume of fluid as per protocol in the form of formula milk at 3‐hourly intervals, while being allowed to continue breastfeeding on‐demand;

• duration of intervention: all infants received the stipulated enteral fluid regimen for 24 hours, after which they were reverted to their usual feeding regimen as before enrolment.

Outcomes

Serum bilirubin

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: μmol/L.

• Direction: lower was better.

• Data value: endpoint.

Rate of decrease of serum bilirubin

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: μmol/L/hour.

• Direction: higher was better.

• Data value: change from baseline.

Number of infants who required exchange transfusion (when the serum bilirubin level remained > 340 µmol/L after commencement of phototherapy)

• Outcome type: dichotomous.

• Reporting: fully reported.

Number of infants with abnormal neurological signs

• Outcome type: dichotomous.

• Reporting: fully reported.

Number of infants with vomiting

• Outcome type: dichotomous.

• Reporting: fully reported.

Number of infants with abdominal distension

• Outcome type: dichotomous.

• Reporting: fully reported.

Identification

Sponsorship source: not stated.

Country: Malaysia.

Setting: NICU of a university hospital.

Comments: study conducted between 1 October 1999 and 30 September 2000.

Author's name: Boo NY.

Institution: Universiti Kebangsaan Malaysia.

Email: [email protected].

Address: Department of Paediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia.

Notes

Rate of decrease in bilirubin reported was indirect and not TSB.

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Unclear risk

Quote: "assignment into groups were based on information previously inserted randomly into sealed envelopes, which were then numbered sequentially."

Unclear from the statements what method was used to generate the random sequence.

Allocation concealment

Unclear risk

Quote: "Assignment into groups was based on information previously inserted randomly into sealed envelopes, which were then numbered sequentially."

Not stated if envelopes used were opaque (therefore, the contents will not be visible) although they were sealed and numbered sequentially.

Blinding of participants and personnel
All outcomes

High risk

Although not clearly stated in paper, blinding appeared highly unlikely as the way of administering fluid differed between the 2 groups, 1 receiving IV supplementation while another receiving enteral supplementation.

Blinding of outcome assessors
All outcomes

Low risk

Authors stated that the laboratory technicians had no knowledge of which fluid regimen was given to which infant.

Incomplete outcome data
All outcomes

Low risk

All 54 randomised infants were included in analyses.

Selective outcome reporting

Low risk

Appeared that all major outcomes as specified in the methods were reported in sufficient detail in the results. We were unable to obtain trial protocol to assess whether there were any further outcomes that were not reported.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation:

• gestational age (mean ± SD): 39.03 ± 0.64 weeks;

• age at admission (mean ± SD): 7.31 ± 1.69 days;

• weight on admission (mean ± SD): 3.10 ± 0.14 kg;

• number of boys (%): 17 (53.1%);

• TSB on admission (mean ± SD): 323.70 ± 29.07 μmol/L.

No fluid supplementation:

• gestational age (mean ± SD): 38.84 ± 0.72 weeks;

• age at admission (mean ± SD): 6.96 ± 1.39 days;

• weight on admission (mean ± SD): 3.09 ± 0.99 kg;

• number of boys (%): 18 (56.2%);

• TSB on admission (mean ± SD): 333.96 ± 18.64 μmol/L.

Inclusion criteria: delivered between 38 and 41 weeks' gestation following an uneventful pregnancy with TSB > 308 μmol/L (18 mg/dL) to < 375 μmol/L (22 mg/dL).

Exclusion criteria: major congenital malformation, haemolytic disease (Rh or ABO incompatibility and a positive Coombs' test), infection (congenital or acquired), G6PD deficiency, dehydration, conjugated hyperbilirubinaemia > 15% of TSB levels, prolonged jaundice persisting beyond 14 days of life.

Pretreatment: no significant differences between groups noted.

Interventions

IV fluid supplementation:

• in addition to breast or formula feeding, received IV fluid supplementation. Received an additional 25% of their maintenance fluid requirement. Daily maintenance fluid level set at 80 mL/kg on day 2, 100 mL/kg on day 3, and 150 mL/kg on day 4 and thereafter. Supplementary fluid given as continuous IV 1/5 normal saline and 5% dextrose.

No fluid supplementation:

• breastfed or formula‐fed (unclear exclusive or mixed) with no IV or oral fluid supplementation.

Outcomes

Serum bilirubin

• Outcome type: continuous.

Number of infants who required exchange transfusion (criteria not stated)

• Outcome type: dichotomous.

Identification

Sponsorship source: none stated.

Country: Iraq.

Setting: neonatal unit of a teaching hospital.

Comments: study conducted from 2 January 2010 to 31 December 2010.

Author's name: Easa ZO.

Institution: author's affiliation not stated in paper.

Email: not provided in paper.

Address: not provided in paper.

Notes

Interventions: text under Methods stated that, "neonates were assigned randomly to two groups, either the breast‐fed or formula‐fed with IV fluid (non‐supplemented group; N=32), or breast‐fed or formula fed in addition to IV fluid (supplemented group; N=32)". Based on abstract and whole manuscript, review author believed that there was a typographical error where the statement should have READ (mistake corrected in bold) "neonates were assigned randomly to two groups, either the breast‐fed or formula‐fed WITHOUT IV fluid (non‐supplemented group; N=32), or breast‐fed or formula fed in addition to IV fluid (supplemented group; N=32)."

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Unclear risk

Quote: "assigned randomly to two groups."

Unclear if allocation sequence was genuinely randomised as authors only stated that "neonates were assigned randomly to two groups."

Allocation concealment

Unclear risk

No information on how and where randomisation was performed to enable an assessment of whether random sequence was generated independently from allocation.

Blinding of participants and personnel
All outcomes

High risk

No mention of blinding in study. As intervention group received IV drip compared to control group (no IV drip), it is highly unlikely that the research personnel were blinded to intervention.

Blinding of outcome assessors
All outcomes

Unclear risk

Not stated if laboratory personnel who tested outcome measures (serum bilirubin) were blinded to the participant's allocation to either intervention or control.

Incomplete outcome data
All outcomes

Low risk

All 64 infants initially randomised were analysed.

Selective outcome reporting

Low risk

Main outcomes which researchers stated in methodology (serum bilirubin levels) were presented adequately in mean and SD for an appropriate length of time (while infants still receiving phototherapy until TSB declined to < 14 mg/dL). Numbers of infants requiring exchange transfusion also described.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation in addition to breastfeeding on‐demand:

• birthweight (mean ± SD): 3321 ± 514 g;

• weight on admission (mean ± SD): 3211 ± 492 g;

• gestation (mean ± SD): 39 ± 1.01 weeks;

• age on admission (mean ± SD): 7.4 ± 3.33 days;

• number of boys (%): 13 (43.3%);

• number of girls (%): 17 (56.7%);

• number with vaginal delivery (%): 18 (60%);

• number with Caesarean delivery (%): 12 (40%).

Breastfeeding on‐demand without fluid supplementation:

• birthweight (mean ± SD): 3258 ± 502 g;

• weight on admission (mean ± SD): 3176 ± 482 g;

• gestation (mean ± SD): 38.9 ± 0.93 weeks;

• age on admission (mean ± SD): 8.8 ± 3.19 days;

• number of boys (%): 18 (60%);

• number of girls (%): 12 (40%);

• number with vaginal delivery (%): 16 (53.3%);

• number with Caesarean delivery (%): 14 (46.7%).

Inclusion criteria: "These neonates were all Iranian race, healthy, breast‐fed, delivered between 38 and 41 weeks of gestation, following an uneventful pregnancy and had a total serum bilirubin (TSB) between 17 and 24.9 mg/dl (291 to 426 μmol/L)."

Exclusion criteria: major congenital malformation, haemolytic disease (Rh or ABO incompatibility and a positive Coombs' test), infection (congenital or acquired), G6PD deficiency, dehydration, conjugated hyperbilirubinaemia > 15% of the TSB levels, and prolonged jaundice persisting beyond 14 days of life.

Pretreatment: no statistical differences in baseline TSB at time of enrolment between groups (P = 0.17).

Interventions

IV fluid supplementation in addition to breastfeeding on‐demand:

• standard fluid protocol: daily maintenance fluid regimen: day 2: 80 mL/kg; day 3: 120 mL/kg; day 4 and thereafter: 150 mL/kg;

• additional fluid: additional 25% of their calculated maintenance fluid volume in addition to breastfeeding on‐demand;

• methods of administration: 1/5 normal saline and 5% dextrose infusion via a peripheral vein;

• duration: 24 hours.

Breastfeeding on‐demand without fluid supplementation:

• standard fluid protocol: daily maintenance fluid regimen: day 2: 80 mL/kg; day 3: 120 mL/kg; day 4 and thereafter: 150 mL/kg;

• additional fluid: no additional fluid on top of breastfeeding on‐demand;

• methods of administration: breastfeeding on‐demand;

• duration: not applicable.

Outcomes

Serum bilirubin

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: μmol/L.

• Direction: lower was better.

• Data value: endpoint.

Number of infants who required exchange transfusion (criteria not stated)

• Outcome type: dichotomous.

Duration of phototherapy

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: hours.

• Direction: lower was better.

• Data value: endpoint.

Rate of decrease in serum bilirubin

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: μmol/L/hour.

• Direction: higher was better.

• Data value: change from baseline.

Identification

Sponsorship source: no information provided.

Country: Iran.

Setting: NICU.

Comments: article identified via the reference list of an included article (Easa 2013). Study conducted between March and October 2003.

Author's name: Iranpour R.

Institution: Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran.

Email: not provided.

Address: Correspondence to: Dr Iraj Haghshenas, Pediatric Department, Al‐Zahra Hospital, Isfahan, Iran.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Unclear risk

Sequence generation not described as there was only a simple statement that, "neonates were assigned randomly" so it is unclear if allocation sequence was genuinely randomised.

Allocation concealment

Unclear risk

No information given to enable an assessment of whether random sequence was generated independently from allocation.

Blinding of participants and personnel
All outcomes

High risk

Although not clearly stated, blinding appeared highly unlikely as 1 group received IV fluid while the other did not.

Blinding of outcome assessors
All outcomes

Unclear risk

No mention if laboratory personnel who measured serum bilirubin levels were blinded to allocation received.

Incomplete outcome data
All outcomes

Low risk

All 60 infants initially randomised were included in analyses.

Selective outcome reporting

High risk

Authors reported only serum bilirubin at different time points. Key clinical outcomes, such as infants with symptoms of bilirubin encephalopathy or kernicterus, infants who required exchange transfusion, or infants who developed adverse effects from IV infusion such as phlebitis were not reported.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

Fluid supplementation:

• gestation (mean ± SD): 37.5 ± 0.8 weeks;

• birth weight (mean ± SD): 2851 ± 473 g;

• cumulative weight loss (mean ± SD): 4.8 ± 3.2%;

• number of boys (%): 29 (78%);

• TSB at inclusion (mean ± SD): 350 ± 31 μmol/L;

• proportion of infants with exclusive breastfeeding (%): 32 (86%).

No fluid supplementation:

• gestation (mean ± SD): 37.8 ± 1.0 weeks;

• birth weight (mean ± SD): 3022 ± 463 g;

• cumulative weight loss (mean ± SD): 4.2 ± 3.0%;

• number of boys (%): 23 (62%);

• TSB at inclusion (mean ± SD): 349 ± 32 μmol/L;

• proportion of infants with exclusive breastfeeding (%): 28 (76%).

Inclusion criteria: term (≥ 37 weeks' gestation) neonates presenting with severe non‐haemolytic hyperbilirubinemia (TSB > 308 mmol/L (18 mg/dL).

Exclusion criteria: infants with TSB > 427 mmol/L (25 mg/dL), acute bilirubin encephalopathy (kernicterus), evidence of haemolysis, obvious signs of dehydration (i.e. sunken fontanel, reduced skin turgor, dry mucosa, tachycardia, delayed capillary refill, excessive weight loss), or major congenital malformations, and receiving IV fluids for any reason.

Pretreatment: no major differences between groups in baseline characteristics.

Interventions

Fluid supplementation:

• IV fluid supplementation with 1/5 saline in 5% dextrose for 8 hours. Volume of supplement included a presumed deficit of 50 mL/kg (equivalent to mild dehydration); half of daily maintenance requirements for an 8‐hour period, in accordance with standard norms; and an extra 20 mL/kg/day as a phototherapy allowance. In addition, infant was allowed breast/formula feeds as given before entry into study. At end of 8‐hour period, hydration status reassessed and IV fluids discontinued. Subsequently, infant continued breast/formula feeds as before and offered 30 mL/kg/day extra oral feeds (expressed breast milk or formula) until discontinuation of phototherapy.

No fluid supplementation:

• infant continued breast/formula feeds ad libitum or as given before the randomisation.

Outcomes

Serum bilirubin

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: μmol/L.

• Direction: lower was better.

• Data value: endpoint.

Rate of decrease of serum bilirubin

• Outcome type: continuous.

• Unit of measure: %.

• Direction: higher was better.

• Data value: change from baseline.

Number of infants who required exchange transfusion

• Outcome type: dichotomous ("exchange transfusion was done if at 4 hours into the study period, TSB increased by > 2 mg/dL (34mmol/L) over the value at the start of the study, or if at 8 hours into the study period, TSB remained at or above 20 mg/dL (342mmol/L)").

Duration of phototherapy

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: hours.

• Direction: lower was better.

• Data value: endpoint.

Number of infants with bilirubin encephalopathy

• Outcome type: dichotomous.

• Reporting: fully reported.

• Unit of measure: number of infants.

• Direction: lower was better.

• Data value: endpoint.

Frequency of breastfeeding in the first 3 days of hospital stay

• Outcome type: continuous.

• Reporting: fully reported (upon request to the author for additional information).

• Unit of measure: number of infants.

• Direction: higher was better.

• Data value: endpoint.

Identification

Sponsorship source: not stated.

Country: India.

Setting: tertiary level NICU.

Comments: study period: September 2003 to June 2004.

Author's name: Dr Praveen Kumar.

Institution: Department of Pediatrics, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Email: [email protected].

Address: Department of Pediatrics, PGIMER, Chandigarh 160012, India.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Low risk

Quote: "Assignment to the various groups was based on stratified block randomisation with variable block size."

Methods of random sequence generation clearly stated.

Allocation concealment

Low risk

Researchers used serially numbered opaque envelopes to assign groups. Envelopes only opened after enrolment.

Blinding of participants and personnel
All outcomes

High risk

In paragraph 2 under discussion, authors stated that, "they could not do complete blinding." It is noted that due to the study design, blinding would be impossible due to different management instituted to groups in which 1 group received IV drip in addition to oral feed as compared to the other group which only received oral feeding.

Blinding of outcome assessors
All outcomes

Low risk

In paragraph 2 of discussion (page 783), authors stated that, "the laboratory personnel performing the serum bilirubin and other biochemical investigations were sent coded samples and were unaware of the group allocation."

Incomplete outcome data
All outcomes

Low risk

All 54 infants enrolled were included in analyses. Number of infants with serum bilirubin levels at 4, 8, and 24 hours were lower than number at inclusion as some infants required exchange transfusion and their serum bilirubin readings were not included.

Selective outcome reporting

Low risk

All major outcomes, including predefined primary outcomes of the number of infants receiving exchange transfusion; duration of phototherapy; % drop in serum bilirubin at 4, 8, and 24 hours of study; and number of infants with bilirubin encephalopathy were reported in sufficient details.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation:

• number of boys (%): 23 (54.76%);

• age (mean): 5.1 days (SD not provided);

• weight on admission (mean ± SD): 2.56 ± 0.14 kg;

• serum bilirubin on admission (mean): 345.42 μmol/L (SD not provided).

No fluid supplementation:

• number of boys (%): 22 (52.38%);

• age (mean): 5.2 days (SD not provided);

• weight on admission (mean ± SD): 2.55 ± 0.18 kg;

• serum bilirubin on admission (mean): 359.1 μmol/L (SD not provided).

Inclusion criteria: term neonates, well‐hydrated, aged 2‐10 days who had indirect non‐haemolytic jaundice with serum bilirubin ≥ 308 μmol/L (18 mg/dL).

Exclusion criteria: jaundice in first day after birth, any manifestations of kernicterus, any form of haemolysis, dehydration, infants with symptoms of dehydration, congenital malformation, taking antibiotics, direct bilirubin > 15% of the total bilirubin, exchange transfusion if it was performed soon after admission (page 2525, column 1, paragraph 2).

Pretreatment: no significant differences between groups in terms of gender, age on admission, weight, and serum bilirubin on admission.

Interventions

IV fluid supplementation:

• breast milk and extra IV fluid including normal saline at 20 mL/kg over 2‐3 hours administered through peripheral vein after admission to hospital.

No fluid supplementation:

• breast milk only.

Outcomes

Rate of decrease of serum bilirubin

• Outcome type: continuous.

• Reporting: partially reported.

• Scale: μmol/L/hour.

• Unit of measure: μmol/L/hour.

• Direction: higher was better.

• Data value: change from baseline.

Number of infants who required exchange transfusion (criteria not stated)

• Outcome type: dichotomous.

Duration of phototherapy

• Outcome type: continuous.

• Reporting: fully reported.

• Unit of measure: hours.

• Direction: lower was better.

• Data value: endpoint.

Identification

Sponsorship source: no information provided.

Country: India.

Setting: NICU of a hospital (level unclear).

Comments: conducted over 6‐month period but the authors did not state the month and year it was conducted.

Author's name: Patel M (first author).

Institution: Civil Hospital, Ahmedabad, India. B. J. Medical College.

Email: not provided.

Address: Department of Pediatrics, B. J. Medical College, Asarwa, Ahmedabad, 380016, Gujarat, India (address for all 3 study authors).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Low risk

Quote: "By using a random number table, simple randomisation was performed."

Methods of sequence generation clearly stated.

Allocation concealment

Unclear risk

No relevant information to enable an assessment of whether allocation was performed independently from random sequence generation.

Blinding of participants and personnel
All outcomes

High risk

Although not mentioned in text, it is highly unlikely that research personnel were blinded due to nature of intervention which was IV fluid compared to enteral feeding only in control group.

Blinding of outcome assessors
All outcomes

Unclear risk

Not stated if laboratory personnel were blinded to the group allocation.

Incomplete outcome data
All outcomes

Low risk

All infants (42 in each group) appeared to have been analysed and their results presented.

Selective outcome reporting

High risk

Rates of decrement of bilirubin in first 6 and first 12 hours presented as means (without SD) as seen in Table 3. Anticipate difficulty obtaining this additional data from authors as corresponding author was not named and there was no email address included. Data for number of infants who required exchange transfusion were adequately reported. Several infants required exchange transfusion but, despite this, there was no report on numbers who developed bilirubin encephalopathy.

Other sources of bias

Low risk

None identified.

Methods

Study design: randomised controlled trial.

Study grouping: parallel group.

Participants

Baseline characteristics

IV fluid supplementation:

• number of boys (%): 27 (54%);

• number of girls (%): 23 (46%);

• age on enrolment (mean ± SD): 7.7 ± 5.12 days;

• birth weight (mean ± SD): 3031.4 ± 484.36 g;

• serum bilirubin level on admission (mean): 362.52 μmol/L (SD not provided).

No fluid supplementation:

• number of boys (%): 24 (48%);

• number of girls (%): 26 (52%);

• age on enrolment (mean ± SD): 7.9 ± 6.8 days;

• birth weight (mean ± SD): 3072.0 ± 430.6 g;

• serum bilirubin level on admission (mean): 359.1 μmol/L (SD not provided).

Inclusion criteria: term, healthy neonate, aged 2‐28 days, serum total bilirubin ≥ 308 μmol/L (18 mg/dL).

Exclusion criteria: jaundice in first day after birth, any manifestations of kernicterus, any form of haemolysis, dehydration, any congenital malformation, treatment with antibiotics, direct bilirubin > 15% of total bilirubin, exchange transfusion if performed soon after admission.

Pretreatment: no major differences in the baseline characteristics between groups.

Interventions

IV fluid supplementation:

• breast milk and extra IV fluid including 1/5 normal saline in 5% dextrose at rate of 80 mL/kg for 2‐day‐old neonate, and an additional 10 mL/kg each day thereafter, to maximum 120 mL/kg through peripheral vein during first 24 hours after admission.

No fluid supplementation:

• breastfeeding on‐demand.

Outcomes

Rate of decrease of serum bilirubin

• Outcome type: continuous.

• Reporting: partially reported.

• Direction: higher was better.

• Data value: change from baseline.

Number of infants who required exchange transfusion (criteria not stated)

• Outcome type: dichotomous.

• Reporting: fully reported.

• Direction: lower was better.

• Data value: endpoint.

Identification

Sponsorship source: not stated.

Country: Iran.

Setting: Paediatric ward of a hospital (level unclear).

Comments: study period: October 2007 to April 2008. Some outcome data reported in a manner that was insufficient for pooling in meta‐analysis. Awaiting reply from study authors.

Author's name: Associate Professor Farhad Heydarian.

Institution: Paediatrics Ward, Ghaem Hospital, Ahmad Abad Ave, Mashhad, Iran.

Email: [email protected].

Address: Paediatrics Ward, Ghaem Hospital, Ahmad Abad Ave, Mashhad, Iran.

Notes

Outcome 'rate of decrease in serum bilirubin' was incompletely reported, as authors only reported median with a single figure given as "confidence interval." We are awaiting further information from study authors.

Risk of bias

Bias

Authors' judgement

Support for judgement

Sequence generation

Low risk

Quote: "By using a random number table, simple randomisation was performed."

Allocation concealment

Unclear risk

Unclear how allocation carried out, in particular, whether allocation performed independently from sequence generation.

Blinding of participants and personnel
All outcomes

High risk

Blinding to care personnel very unlikely as 1 group of infants received additional IV fluid while another group did not.

Blinding of outcome assessors
All outcomes

Unclear risk

Unclear whether assessors of laboratory outcomes were blinded to allocation status of infants.

Incomplete outcome data
All outcomes

Low risk

Appeared that all 100 infants randomised included in report for major outcomes of number of infants who required exchange transfusion and rate of decrease in serum bilirubin in first 24 hours.

Selective outcome reporting

High risk

The outcome 'Rate of decrease of serum bilirubin in the first 24 hours after admission' was incompletely reported, as authors only provided median figures with a single figure given for confidence interval (we are waiting study author's response to our request for these data). Study authors did not include any data on adverse events of IV fluids such as thrombophlebitis. Number of infants with bilirubin encephalopathy not reported.

Other sources of bias

Low risk

None identified.