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Antenatal dietary advice and supplementation to increase energy and protein intake

  1. Erika Ota1,*,
  2. Ruoyan Tobe-Gai2,
  3. Rintaro Mori3,
  4. Diane Farrar4

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 12 SEP 2012

DOI: 10.1002/14651858.CD000032.pub2


How to Cite

Ota E, Tobe-Gai R, Mori R, Farrar D. Antenatal dietary advice and supplementation to increase energy and protein intake. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD000032. DOI: 10.1002/14651858.CD000032.pub2.

Author Information

  1. 1

    Graduate School of Medicine, The University of Tokyo, Department of Global Health Policy, Tokyo, Japan

  2. 2

    School of Public Health, Shandong University, Jinan, China

  3. 3

    National Center for Child Health and Development, Department of Health Policy, Tokyo, Tokyo, Japan

  4. 4

    Bradford Institute for Health Research, Maternal and Child Health, Bradford, UK

*Erika Ota, Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0011, Japan. e-i@umin.ac.jp.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 12 SEP 2012

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This is not the most recent version of the article. View current version (02 JUN 2015)

 
Characteristics of included studies [ordered by study ID]
Blackwell 1973

MethodsInterventions 'assigned randomly and blindly', but method not specified.


ParticipantsWell-nourished rural Taiwanese women with 'marginal' diets (estimated daily energy intake is approximately 2000 kcal and protein intake <= 40 g for adult women in this area from preliminary food survey in 1965).


InterventionsExperimental: chocolate-flavoured liquid supplement given twice daily beginning after prior birth and continuing during index pregnancy; supplement contained 40 g protein and 800 kcal energy plus vitamins/minerals.
Control: supplement containing vitamins and minerals only, but given at same times and for same duration.


OutcomesGestational weight gain, preterm birth, birthweight, small-for-gestational age, length, head circumference, and IQ at age 5.


Notes1) Data presented on dietary substitution, but based on meal survey only.
2) High alleged net energy supplement not associated with significantly higher gestational weight gain.
3) Discrepancies in first-infant LBW rates in 1981 vs 1973 reports.
4) Significant correlation between birthweight and energy (and supplement) intake in controls only.
5) Supplementation continued until 15 months postpartum; data on maternal postpartum weight therefore, omitted from review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAlthough details are not described, it says the study participants were randomly assigned.

Allocation concealment (selection bias)Unclear riskInsufficient information, the method of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Low riskThe 2 supplements were similar and no women were considered to be able to distinguish them.

Incomplete outcome data (attrition bias)
All outcomes
Low risk506 out of 524 (96.5%) were with complete data for the analysis and this was not ITT.

Selective reporting (reporting bias)Unclear riskNo description on this. Not mentioned on registered protocol.

Other biasUnclear riskNo data were provided for background characteristics.

Briley 2002

MethodsRandomisation method not reported.


Participants27 low-income African-American women. Mean pre-pregnancy body mass index is within the normal range for both groups (intervention, 24.7±3.4, control, 23.2 ±4.1 kg/m2)


InterventionsExperimental: minimum of 6 individualised in-home nutrition assessment and counselling visits.
Control: 2 home visits without counselling.


OutcomesEnergy intake, gestational weight gain, birthweight, and preterm birth.


Notes1) 7 of 27 randomised women dropped out and not included in analysis.
2) Neither participants nor observers apparently blind to allocation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskWomen were randomly assigned, though no detailed methods on randomisation were described.

Allocation concealment (selection bias)Unclear riskInsufficient information, the method of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Low riskCounselling group is evident and interventions could not be blinded.

Incomplete outcome data (attrition bias)
All outcomes
High risk7 women dropped out of 27 women (74.1%) and no ITT.

Selective reporting (reporting bias)Unclear riskUncertain, as if the protocol was registered, etc. was not described.

Other biasLow riskThere was no significant difference in demographic background between the groups.

Ceesay 1997

MethodsCluster randomisation by village "using a stratified design according to village size", but no details provided on method of random allocation or concealment.


ParticipantsRural Gambian women from 28 villages with "chronically" marginal nutrition. Undernutrition more pronounced from June to October (the 'hungry' season involving low food supply and heavy agricultural work) than from November to May (the dry harvest season with adequate food supply and less strenuous work).The mean maternal body mass index measured after delivery was 20.7± 2.3 kg/m2 in the control group and 21.3 ± 2.8 kg/m2 in the intervention group.


InterventionsExperimental villages: 2 supplement biscuits containing roasted groundnuts, rice flour, sugar, and groundnut oil (4250 kJ (1017 kcal) energy, 22 g protein, 56 g fat, 47 mg calcium, and 1.8 mg iron)] consumed daily in presence of birth attendants. Supplementation began at 20 weeks' gestation.
Control villages: no supplement.


OutcomesGestational weight gain, GA, birthweight, birth length, head circumference, stillbirth, and neonatal death.


Notes1) Randomisation by cluster (village), but effects reported for individual births, based on multilevel (3-stage random-effects) modelling with separate error terms for village, mother, and (for mothers with more than 1 pregnancy during study) baby.
2) Results reported both overall and stratified by season (hungry vs harvest), but this review based on overall data. Note that definitions of seasons are not entirely consistent with previous (non-randomised) studies from this group and were chosen because 'post hoc analysis indicated that this selection yielded the greatest discrimination between hungry and harvest season effects'.
3) Many outcome analyses are based on individual women and therefore, do not account for the intra-class correlation among women living in the same village. Sample sizes in these outcomes have therefore, been adjusted downward to the nearest integer by dividing by 1+(m-1)r, where m is the average number of women per village and r = 0.01 is the (assumed) intra-class correlation co-efficient.

4) Data on LBW used in analysis of infant born small-for-gestational age.
5) Number of intervention and control participants reversed in column headings of Table 5.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskVillages were randomly assigned, but no details provided on method of random allocation.

Allocation concealment (selection bias)Unclear riskInsufficient information, the method of allocation concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
High riskThe supplement biscuits provided in intervention group only. Intervention was evident.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOver 95% agreed and remained in the trial throughout,The analysis presented here covers 2047 normal singleton live births from 1460 different women who delivered during October 1989 to October 1994.

Selective reporting (reporting bias)Unclear riskNot clear if the protocol was registered prior to the study.

Other biasLow riskSimilar between the groups and multilevel multiple regression was employed.

Elwood 1981

MethodsRandomisation based on random numbers with sealed envelopes.


Participants1251 pregnant Welsh women in 2 small towns recruited at time of first reporting of pregnancy in South Wales, UK. No information available for pregnant women's pre-pregnancy BMI.


InterventionsExperimental: free tokens worth ½ pint milk each.
Control: no intervention.


OutcomesGA, preterm birth, birthweight, LBW, length, and head circumference.


Notes1) 24% of women lost to follow-up, with evidence of higher losses in control group.
2) No adjustment for higher percentage of smokers in control group.
3) Trial also includes postnatal milk supplement (tokens) in children; all data on postnatal growth in children therefore, omitted from review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation based on random numbers with sealed envelopes.

Allocation concealment (selection bias)Low riskRandomisation based on random numbers with sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes
High riskAllocation was evident.

Incomplete outcome data (attrition bias)
All outcomes
Low risk212 were loss of follow-up. 82% were analysed.

Selective reporting (reporting bias)Unclear riskNot enough information was provided.

Other biasUnclear riskNot enough information was provided.

Girija 1984

MethodsRandomly allocated.


Participants20 poor Indian women in last trimester. Pregnant women's weight at last trimester was approximately 47 kg in both intervention group and control group.


InterventionsExperimental: supplement containing 50 g sesame cake, 40 g jaggery, and 10 g oil (417 kcal energy and 30 g protein).
Control: normal (unsupplemented) diet.


OutcomesGestational weight gain, birthweight, length, head circumference, breast milk output, and weight, length, and head circumference, through 3 months of age.


Notes1) Large losses to follow-up for breast milk output.
2) No SDs reported on postnatal anthropometric outcomes, so data not included in review.
3) No data reported on compliance or dietary substitution.
4) Energy and protein intakes appear higher before supplementation, even in supplemented group.
5) Mean GA (between 36 and 37 weeks in both groups) is incompatible with reported rates of preterm birth (0 of 10 in both groups), so data on preterm birth are omitted from review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe participants were randomly assigned though no other details were provided.

Allocation concealment (selection bias)Unclear riskInsufficient information, the method of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
High riskThe allocation was evident.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information was given.

Selective reporting (reporting bias)Unclear riskNo enough information was given.

Other biasUnclear riskNo description on demographic characteristics and others.

Hunt 1976

MethodsMethod of randomisation not reported.


Participants344 Spanish-speaking women with first prenatal clinic visit <= 21 weeks' gestation in Los Angeles. Pre-pregnancy self-report weight for intervention group was 127 ± 19 lb, and control group was 126 ± 23 lb.


InterventionsExperimental: nutrition classes (average of 3 per woman). Control: no classes.


OutcomesProtein and energy intakes; no data on gestational weight gain or pregnancy outcome.


Notes1) 65 women excluded or lost (not interviewed) post-randomisation.
2) Possible 'contamination' via contact between women in 2 groups.
3) No blinding.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe women were randomly assigned to a control or treatment group. Method of randomisation not reported.

Allocation concealment (selection bias)Unclear riskInsufficient information, the method of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding, possible ‘Contamination’ via contact between women in the groups.

Incomplete outcome data (attrition bias)
All outcomes
Low risk279 (81%) women were followed. Reasons for missing outcome data balanced in numbers across groups.

Selective reporting (reporting bias)Unclear riskNo protocol, insufficient information to permit judgement.

Other biasUnclear riskInsufficient information to assess whether an important risk of bias exist.

Huybregts 2009

MethodsA non-blinded,  individually randomised controlled trial. A randomisation scheme was generated by a computer program in permuted blocks of 4. Randomisation numbers were sealed in opaque envelopes by administrative staff.


Participants1296 Pregnant women in 2 villages In rural Burkina Faso. BMI at entry of the trial for intervention group was 20.8 ± 2.2 kg/m2, and control group was 21.0 ± 2.2 kg/m2.


InterventionsIntervention: prenatal multiple micronutrient (MMN) + fortified food supplement (FFS) Control: MMN.


OutcomesAnthropometric measures at birth, LBW, infant born small-for-gestational age, LGA, GA, preterm.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA randomisation scheme was generated by a computer program in permuted blocks of 4. Randomisation numbers were sealed in opaque envelopes by administrative staff.

Allocation concealment (selection bias)Low riskSequentially numbered, opaque, sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding but care was taken to blind staff who performed the anthropometric measurements at delivery; measurement bias was therefore unlikely.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAnalysis for 87% of the 1175 live singleton deliveries enrolled.

Selective reporting (reporting bias)Low riskThe trial was registered at clinical trials.gov as NCT00909974.

Other biasLow riskThe compliance was closely verified by using a community-based network of home visitors.

Kafatos 1989

MethodsRandomisation of 20 clinics using computer-generated random numbers.


Participants568 pregnant women in rural area in Northern Greece < 27 weeks' gestation. Initial BMI was 23.10 ± 0.2 kg/m2in intervention group, and 22.7 ± 0.2 kg/m2 in control group.


InterventionsExperimental: nutrition counselling to improve 'quality' of diet ('high nutrient value'). Control: no counselling.


OutcomesEnergy and protein intake, serum vitamin and mineral levels, gestational weight gain, birthweight, birth length and head circumference, GA, LBW, infant born small-for-gestational age, preterm birth, stillbirth, and neonatal death.


Notes1) Analysis based on individual women, rather than clinic. To account for the intra-class correlation among women attending the same clinic, sample sizes have been adjusted downward to the nearest integer by dividing by 1+(m-1)r, where m is the average number of women per clinic (30.0 intervention and 26.8 control) and r = 0.01 is the (assumed) intra-class correlation.
2) Dietary intake unblinded, and energy intake higher in experimental group prior to intervention.
3) Inconsistent results: lower preterm rate, yet no difference in mean GA; higher head and chest circumferences but no difference in birthweight.
4) Discrepancies in sample sizes for different outcomes, even birthweight vs LBW rate.
5) SEM of GA in intervention (experimental) group assumed to be 0.10, not the 0.01 shown in Table 3.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA cluster randomisation of 20 clinics using computer-generated random numbers.

Allocation concealment (selection bias)Low riskRandomisation by clinic using computer-generated random numbers, clinic enrolled all women to minimise selection bias for allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding but the possible contamination effects of the educational program in that women from the same village or neighbourhood attending the same clinic would be enrolled in the same group.

Incomplete outcome data (attrition bias)
All outcomes
Low riskFor dietary records, Intervention group 216 (86.7%), control group 180(94.2%) were followed up after allocation.

Selective reporting (reporting bias)Unclear riskInsufficient information to permit judgement.

Other biasHigh riskEnergy intake higher in experimental group prior to intervention.

Kardjati 1988

Methods"Blind" randomisation based on household numbers, with use of random-numbers table.


Participants747 women in 3 villages in rural East Java (an area known to be 'nutritionally vulnerable'(Kardjati 1983) at 26-28 weeks' gestation. Total mean ± SD pre-pregnant BMI was 18.7 ± 2.0 kg/m2.


InterventionsExperimental: supplement containing a dry powder (50% fat, 10% casein, and 40% glucose) providing 465 kcal energy and 7.1 g protein ('high energy').
Control: supplement containing 52 kcal energy and 6.2 g protein ('low energy').


OutcomesGestational weight gain, birthweight, and breast milk output.


Notes1) Although data on birthweight were not analysed according to ITT, they are included in this review because birthweight was similar in the 2 study groups and in non-compliers (both groups combined).
2) Data on gestational weight gain are based on the combined results in all 3 compliance strata but are missing for approximately one-third of study participants.
3) Data on breast milk output based on a selection of 50% of 'randomly'-selected study participants (only 10% of total study sample). Data excluded on 16 'uncooperative' or 'repeatedly absent' participants.
4) Data on postnatal infant growth reported in Kusin 1992 have been excluded from review, because poor compliers were excluded from the analysis (i.e., not based on ITT).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskThe household numbers were the basis for allocation using random number tables.

Allocation concealment (selection bias)Low riskUsing random number tables.

Blinding (performance bias and detection bias)
All outcomes
Low riskWhile the study was not blind, the randomisation was, since the characteristics of the pregnant women cannot be inferred from the household numbers.

Incomplete outcome data (attrition bias)
All outcomes
High riskBirthweight was recorded in 419 liveborn singletons (87%).

Gestational weight gain is missing for approximately one-third of study participants.

Selective reporting (reporting bias)Unclear riskProtocol not available.

Other biasHigh riskThe absence of a difference in mean birthweight between the HE and LE groups as a whole may be attributed to a masking effect of the better home diet in the experimental period.

Mora 1978

MethodsAllocation method not reported.


Participants456 poor first-or second-trimester women from Bogota slum for whom at least 50% of previous children had weight-for-height < 85% of Colombian standard. No information about maternal anthropometry (weight or BMI) provided.


InterventionsExperimental: supplement containing 60 g dried skim milk, 150 g enriched bread, and 20 g vegetable oil (856 kcal energy and 38.4 g protein) beginning in third trimester.
Control: normal (unsupplemented) diet.


OutcomesPre-eclampsia, GA, preterm birth, birthweight, LBW, stillbirth, perinatal mortality, neonatal mortality.


Notes1) Compliance assessed but data not presented.
2) Substitution assessed by single 24-hour recall 8 weeks after starting supplement.
3) Preterm birth rate not increased, but higher mortality reported among those born preterm.
4) Data on term LBW used in analysis of infant born small-for-gestational age.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomly assigned either to a supplemented or an unsupplemented group.

Allocation concealment (selection bias)Unclear riskAllocation method not reported.

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskSupplemented group (186/226, 82.3%), unsupplemented group(173/230, 75.2%) were followed. Total sample and subsample in table2 showed no significant difference in characteristics.

Selective reporting (reporting bias)Unclear riskNo protocol available, insufficient information to judge this.

Other biasHigh riskCompliance not mentioned.

Ross 1985

MethodsAllocation method not reported.


Participants127 Black South African women < 20 weeks' gestation.Study women averaged > 70 kg at 20 weeks.


InterventionsExperimental: supplement containing 700-800 kcal energy and 36-44 g protein. 2 types of supplements were given: a high-bulk mixture of beans and maize, given as mush with added vitamins, and a low-bulk porridge containing dried skimmed milk, maize, flour, vitamins, and minerals; the high- and low-bulk groups are combined in the experimental group for this review.
Control: placebo pills (zinc-supplemented group is excluded from review).


OutcomesGestational weight gain (after 20 weeks), GA, and birthweight.


Notes1) Higher gestational weight gain in control group argues against causal association with birthweight.
2) No data presented on compliance or substitution.
3) Number of women originally randomised not reported ('90% continued ... to delivery').
4) Original sample size not given nor its justification.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk127 Zuru women were randomly assigned to 4 groups.

Allocation concealment (selection bias)Unclear riskAllocation method not reported.

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNumber of women originally randomised not reported, or no missing case.

Selective reporting (reporting bias)Unclear riskProtocol is not available.

Other biasHigh riskNo data presented on compliance or substitution.

Rush 1980

MethodsStratified randomisation based on table of random numbers, with allocation in sealed envelope and blinding of all research staff.


Participants1051 low-income black women in Harlem (New York City) <= 30 weeks' gestation 'at risk' for LBW based on 1 or more of the following criteria: 1) pre-pregnancy weight < 110 lbs; 2) pre-pregnancy weight 110-139 lbs plus low gestational weight gain as of recruitment;
3) pre-pregnancy weight 110-139 lbs plus previous history of LBW; or
4) pre-pregnancy weight 110-139 lbs plus protein intake < 50 grams in the 24 hours preceding registration.


InterventionsExperimental (1): balanced energy/protein 16-oz beverage supplement containing 322 kcal energy, 6 g protein, and vitamins/minerals ('complement').
Experimental (2): high-protein 16-oz beverage supplement containing 470 kcal + 40 g protein per day + vitamins and minerals.
Control: supplement containing vitamins/minerals only.


OutcomesGestational weight gain, GA, preterm birth, infant born small-for-gestational age, birthweight, LBW, stillbirth, neonatal mortality, and weight, length, head circumference, and Bayley scores at 1 year.


NotesAlmost no data presented on the (approximately) 25% of participants who failed to comply, dropped out, or moved away.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom assignment.

Allocation concealment (selection bias)Low riskBased on table  of random numbers, with allocation in sealed envelope.

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinding of all research staff.

Incomplete outcome data (attrition bias)
All outcomes
Low risk94% follow-up, 48 whose mothers chose to discontinue supplements and 1 infant with Down’s syndrome excluded.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskAlmost no data presented on the (approximately) 25% of participants who failed to comply, dropped out, or moved away.

Sweeney 1985

MethodsStratified randomisation 'using biased coin methodology'.


Participants47 healthy women < 20 weeks' gestation in Salt Lake, USA. Maternal height ranged from 152 to 180 cm, and pre-pregnant weight ranged from 41 to 113 kg.


InterventionsExperimental: Higgins' method of protein/energy 'prescription' (i.e., advice only, no supplementation) Control: no advice.


OutcomesProtein and energy intake, gestational weight gain, birthweight, and GA.


Notes1) Slight discrepancy in number of women allocated.
2) Mean and SD weight gain, birthweight, and GA not reported by allocation group.
3) Probable non-blinding of intake (protein and energy) histories.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStratified random allocation using a biased coin methodology.

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement for allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
High riskProbable non blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low risk43 out of 47 (91.5%) were analysed.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskSlight discrepancy in number of women allocated.

Viegas 1982a

MethodsAllocation method not reported.


Participants153 Asian women in Birmingham, UK < 20 weeks' gestation who appeared well-nourished based on their weight and height. The mean ± SD height and weight for intervention group was 154.6 ± 4.4 cm, 53.0 ± 9.1 kg and control group was 156.5 ± 5.8 cm, 56.3 ± 10.6 kg.


InterventionsExperimental: supplement of flavoured carbonated glucose drink providing 273 kcal energy (with 11% of energy as protein) plus vitamins from 18 to 38 weeks.
Control: supplement of flavoured carbonated water containing iron and vitamin C.


OutcomesGestational weight gain and birthweight, placental weight, maternal skin folds and arm circumference.


Notes1) Designed as 3-arm trial, but group receiving supplement with 11% of energy provided as protein combined with energy-only group for this review.
2) No evidence that study women were undernourished.
3) No data presented on compliance or dietary substitution.
4) Results presented only in graphic form; extracted data are therefore approximate.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMinimisation. Allocation to a particular regimen was designed to give as closely as possible the same distribution of parity, abnormal past obstetric history and history of early bleeding in the current pregnancy.

Allocation concealment (selection bias)Unclear riskAllocation method not reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskProtein energy vitamin group: 47/51(92.1%), energy vitamin group: 50/57(87.7%), vitamin group 45 no missing.

Selective reporting (reporting bias)Unclear riskNo protocol available.

Other biasHigh riskNo data presented on compliance.

Viegas 1982b

MethodsAllocation method not reported.


Participants130 Asian women in Birmingham, UK < 20 weeks' gestation (who appeared well-nourished (based on height and weight) prior to pregnancy, 45 of whom were later considered "nutritionally at risk" based on inadequate increase in triceps skin folds between 18 and 28 weeks) stratified at 28 weeks according to increase in triceps skinfold during second trimester (<= 0.02 vs > 0.02 mm/week).


InterventionsExperimental: supplement of flavoured carbonated glucose drink + skim milk powder providing 425 kcal energy (with 10% of energy as protein), plus vitamins from 28 to 38 weeks.
Control: supplement of flavoured carbonated water containing iron and vitamin C.


OutcomesGestational weight gain, GA, birthweight, length, and head circumference, placental weight, and maternal skin folds.


Notes1) Designed as 3-arm trial, but group receiving supplement with 10% of energy provided as protein combined with energy-only group for this review.
2) No data presented on compliance or dietary substitution.
3) Results for gestational weight gain presented only in graphic form; extracted data are therefore approximate.
4) Probable misprint in Table II: mean GA in supplemented (EnVi = energy plus vitamins) group assumed to be 39.2 weeks, rather than the 29.2 weeks indicated in the table.
5) Data on outcomes stratified according to increase in triceps skin folds from 18-28 weeks. Because of harmful effect in those with normal skin folds and no statement that threshold was established a priori, outcomes from both strata have been combined in review.
6) Data from ITT analysis extracted from graph; not presented in tabular form.
7) Probable misprint in GA for control group (adequate skinfold stratum) in Table II.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMembers of each group were then assigned at random to 1 of 3 supplement groups.

Allocation concealment (selection bias)Unclear riskAllocation method not reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 2 missing in EnVi group, reason for perinatal death with detailed. 128 out of 130 (98.5%)

Selective reporting (reporting bias)Unclear riskProtocol not available.

Other biasHigh riskNo data for compliance.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aaltonen 2005Intervention involved advice to alter fat composition of the diet, but not to change its energy or protein content.

Adams 1978Participants were high-risk women only.

Anderson 1995The nutritional advice studied does not relate to energy or protein intake, or both.

Atton 1990Not randomised, alternate allocation.

Badrawi 1993The current inclusion of information about caloric restriction for women who are overweight or obese only serves to increase confusion as it requires discussion of the clinical implications for 2 different populations, thus we excluded the outcome of "energy and protein restriction in women who were overweight or showed high weight gain". This trial previously included in the analysis, have now been excluded because the target population was out of focus.

Campbell 1975The current inclusion of information about caloric restriction for women who are overweight or obese only serves to increase confusion as it requires discussion of the clinical implications for 2 different populations, thus we excluded the outcome of "energy and protein restriction in women who were overweight or showed high weight gain". This trial previously included in the analysis, have now been excluded because the target population was out of focus.

Campbell 1983The current inclusion of information about caloric restriction for women who are overweight or obese only serves to increase confusion as it requires discussion of the clinical implications for 2 different populations, thus we excluded the outcome of "energy and protein restriction in women who were overweight or showed high weight gain". This trial, previously included in the analysis, has now been excluded because the target population was out of focus.

Campbell Brown 1983Not randomised, alternate allocation.

Clapp 1997Experimental intervention involved no change in energy or protein intake, but only in the type of carbohydrate in the diet. Moreover, the only outcomes studied were glycaemic (blood glucose) responses to diet and exercise.

Dirige 1987The nutritional advice studied does not relate to energy or protein intake, or both.

Ebbs 1941Not randomised.

Eneroth 2010Follow-up analysis of Matlab (MINIMat) study, intervention is not relevant to our review.

Fard 2004RCT of maternal dietary fat modification with no net supplementation of energy or protein.

Fung 2010Participants are not only pregnant women and outcome is not relevant to our review.

Guelinckx 2010The current inclusion of information about caloric restriction for women who are overweight or obese only serves to increase confusion as it requires discussion of the clinical implications for 2 different populations, thus we excluded the outcome of "energy and protein restriction in women who were overweight or showed high weight gain". This trial previously included in the analysis, have now been excluded because the target population was out of focus.

Hankin 1962Not randomised, allocation by day of week.

Iyengar 1967Not randomised.

Kaseb 2002Not randomised, quasi-randomised study.

Kinra 2008Intervention was not randomised and included both prenatal and postnatal (for the infant/child) supplementation.

Lechtig 1975Despite the original RCT design, the reported results were based on observational analyses of the data. In 1 report of this trial (Delgado 1982), the results were indeed presented according to randomised treatment. This report was also excluded, however, because the analysis was based on individual women despite randomisation by village, was limited to women with data on length of gestation, and showed evidence of major problems in validity of gestational age measurements. Stein 2003, Webb 2005, Stein 2006, and Hodinott 2008 were also based on the treatment allocation as randomised but were excluded from analysis of long-term outcomes because the offspring were also supplemented, making it impossible to distinguish effects of prenatal maternal supplementation from those of postnatal supplementation of the infant/child.

Luke 2001Not randomised or quasi-randomised trial.

Mardones 1988Not randomised, alternate allocation.

Metcoff 1985Participants were high-risk women only.

Moses 2006RCT of diets with high vs low glycaemic index, with no net supplementation of energy or protein.

Qureshi 1973Not randomised, alternate allocation.

Ross 1938Not randomised, alternate allocation.

Tompkins 1954The target population was out of focus.

Tontisirin 1986Not randomised.

Wolff 2008The current inclusion of information about caloric restriction for women who are overweight or obese only serves to increase confusion as it requires discussion of the clinical implications for 2 different populations, thus we excluded the outcome of "energy and protein restriction in women who were overweight or showed high weight gain". This trial previously included in the analysis, have now been excluded because the target population was out of focus.

Woods 1995Small (n = 10) cross-over trial of high- vs low-protein diet without control group, but no pregnancy or offspring outcomes are analysed. The only outcomes reported are renal haemodynamic responses to a meat meal.

 
Characteristics of ongoing studies [ordered by study ID]
Moore 2011

Trial name or titleInvestigating the effects of pre-natal and infancy nutritional supplementation on infant immune development in The Gambia: the early nutrition and immune development (ENID) trial.

Methods3-way randomised controlled trial 

ParticipantsWomen (aged 18 to 45 years) resident in Kiang West Region, The Gambia, with pregnancy confirmed by urine test and ultrasound examination and with gestational age approximately 10-20 weeks. 

Interventions4 pregnancy interventions, to be given daily from 12 weeks' gestation until delivery: 
1. FeFol: iron-folate, 60 mg iron 400 µg folate, representing the usual standard of care during pregnancy, as per Gambian Government guidelines (control group). 
2. Multiple micronutrients: a combination of 15 micronutrients, specifically designed for use during pregnancy, and as formulated by UNICEF. A single tablet provides the recommended dietary allowance for each micronutrient, but we will supplement women in this arm of the trial with 2 daily MMN tablets. 
3. PE + FeFol: protein-energy and iron-folate. A food-based supplement developed by Valid International, providing a comparable level of iron and folate to the FeFol only arm, but with the addition of energy, protein and lipids. 
4. PE + MMN: protein-energy and multiple micronutrients. A micronutrient fortified food-based supplement also developed by Valid International, and providing comparable levels of micronutrients to the MMN arm (including FeFol), in addition to the energy and protein and lipid content. 

OutcomesInfant immunity development

Starting date01/10/2009

Contact informationDr  Sophie  Moore

smoore@mrc.gm

NotesISRCTN49285450, Anticipated end date 30/09/2013

 
Comparison 1. Nutritional advice during pregnancy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Stillbirth1431Risk Ratio (M-H, Fixed, 95% CI)0.37 [0.07, 1.90]

 2 Neonatal death1448Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.35, 4.72]

 3 Birthweight (g)2426Mean Difference (IV, Random, 95% CI)205.75 [-242.54, 654.03]

 4 Birth length (cm)1399Mean Difference (IV, Fixed, 95% CI)0.17 [-0.72, 1.06]

 5 Birth head circumference (cm)1389Mean Difference (IV, Fixed, 95% CI)0.99 [0.43, 1.55]

 6 Small-for-gestational age1404Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.45, 2.11]

 7 Preterm birth2449Risk Ratio (M-H, Fixed, 95% CI)0.46 [0.21, 0.98]

 8 Gestational age (week)1399Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.48, 0.28]

 9 Protein intake (g/day)3632Mean Difference (IV, Fixed, 95% CI)6.99 [3.02, 10.97]

 10 Energy intake (kcal/day)3342Mean Difference (IV, Fixed, 95% CI)105.61 [-18.94, 230.15]

 11 Total gestational weight gain (kg)2Mean Difference (IV, Random, 95% CI)Totals not selected

 
Comparison 2. Balanced protein/energy supplementation in pregnancy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Stillbirth53408Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.40, 0.98]

 2 Neonatal death53381Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.43, 1.07]

 3 Birthweight (g)115385Mean Difference (IV, Random, 95% CI)40.96 [4.66, 77.26]

    3.1 Undernourished women
82903Mean Difference (IV, Random, 95% CI)66.96 [13.13, 120.78]

    3.2 Adequately nourished women
62482Mean Difference (IV, Random, 95% CI)15.93 [-20.83, 52.69]

 4 Birth length (cm)53370Mean Difference (IV, Fixed, 95% CI)0.16 [0.01, 0.31]

 5 Birth head circumference (cm)53352Mean Difference (IV, Random, 95% CI)0.04 [-0.08, 0.17]

 6 Small-for-gestational age74408Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.69, 0.90]

 7 Preterm birth53384Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.80, 1.16]

 8 Gestational age (week)63471Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.22, 0.01]

 9 Weekly gestational weight gain (g/week)92391Mean Difference (IV, Random, 95% CI)18.63 [-1.81, 39.07]

 10 Pre-eclampsia2463Risk Ratio (M-H, Fixed, 95% CI)1.48 [0.82, 2.66]

 11 Bayley mental score at 1 year1411Mean Difference (IV, Fixed, 95% CI)-0.74 [-1.95, 0.47]

 12 IQ at 5 years1153Mean Difference (IV, Fixed, 95% CI)0.0 [-4.98, 4.98]

 13 Weight at 1 year (g)2623Mean Difference (IV, Fixed, 95% CI)30.43 [-139.67, 200.53]

 14 Length at 1 year (cm)1428Mean Difference (IV, Fixed, 95% CI)0.0 [-5.69, 5.69]

 15 Head circumference at 1 year (cm)2627Mean Difference (IV, Fixed, 95% CI)-0.13 [-0.35, 0.10]

 16 Duration of labour (hours)1345Mean Difference (IV, Fixed, 95% CI)-0.09 [-1.18, 1.00]

 17 Maternal weight 4 weeks' postpartum (kg)1354Mean Difference (IV, Fixed, 95% CI)-0.90 [-1.92, 0.12]

 18 Height at age 11-17 years (cm)1855Mean Difference (IV, Fixed, 95% CI)-0.39 [-1.73, 0.94]

    18.1 Boys
1445Mean Difference (IV, Fixed, 95% CI)0.60 [-1.40, 2.60]

    18.2 Girls
1410Mean Difference (IV, Fixed, 95% CI)-1.20 [-3.00, 0.60]

 19 Weight at 11-17 years (kg)1855Mean Difference (IV, Fixed, 95% CI)0.46 [-0.77, 1.69]

    19.1 Boys
1445Mean Difference (IV, Fixed, 95% CI)0.70 [-0.89, 2.29]

    19.2 Girls
1410Mean Difference (IV, Fixed, 95% CI)0.10 [-1.86, 2.06]

 20 Systolic blood pressure at age 11-17 years (mmHg)1855Mean Difference (IV, Fixed, 95% CI)0.60 [-0.61, 1.81]

    20.1 Boys
1445Mean Difference (IV, Fixed, 95% CI)1.10 [-0.61, 2.81]

    20.2 Girls
1410Mean Difference (IV, Fixed, 95% CI)0.10 [-1.60, 1.80]

 21 Diastolic blood pressure at age 11-17 years (mmHg)1855Mean Difference (IV, Fixed, 95% CI)-0.08 [-1.10, 0.93]

    21.1 Boys
1445Mean Difference (IV, Fixed, 95% CI)0.5 [-0.98, 1.98]

    21.2 Girls
1410Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.99, 0.79]

 22 BMI z-score at age 11-17 years1855Mean Difference (IV, Fixed, 95% CI)0.16 [0.01, 0.31]

    22.1 Boys
1445Mean Difference (IV, Fixed, 95% CI)0.20 [0.00, 0.40]

    22.2 Girls
1410Mean Difference (IV, Fixed, 95% CI)0.10 [-0.13, 0.33]

 23 % body fat at 11-17 years1847Mean Difference (IV, Fixed, 95% CI)0.06 [-0.41, 0.52]

    23.1 Boys
1440Mean Difference (IV, Fixed, 95% CI)0.0 [-0.54, 0.54]

    23.2 Girls
1407Mean Difference (IV, Fixed, 95% CI)0.20 [-0.68, 1.08]

 
Comparison 3. High protein supplementation in pregnancy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Stillbirth1529Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.31, 2.15]

 2 Neonatal death1529Risk Ratio (M-H, Fixed, 95% CI)2.78 [0.75, 10.36]

 3 Small-for-gestational age1505Risk Ratio (M-H, Fixed, 95% CI)1.58 [1.03, 2.41]

 4 Birthweight (g)1504Mean Difference (IV, Fixed, 95% CI)-73.0 [-171.26, 25.26]

 5 Preterm birth1505Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.83, 1.56]

 6 Weekly gestational weight gain (g/week)1486Mean Difference (IV, Fixed, 95% CI)4.5 [-33.55, 42.55]

 7 Weight at 1 year (g)1409Mean Difference (IV, Fixed, 95% CI)61.0 [-184.60, 306.60]

 8 Length at 1 year (cm)1412Mean Difference (IV, Fixed, 95% CI)0.20 [-5.59, 5.99]

 9 Head circumference at 1 year1412Mean Difference (IV, Fixed, 95% CI)0.11 [-0.19, 0.41]

 10 Bayley mental score at 1 year1396Mean Difference (IV, Fixed, 95% CI)0.32 [-0.91, 1.55]

 
Comparison 4. Isocaloric balanced protein supplementation in pregnancy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Birthweight (g)2184Mean Difference (IV, Random, 95% CI)108.25 [-220.89, 437.40]

 2 Weekly gestational weight gain (g/week)2184Mean Difference (IV, Random, 95% CI)110.45 [-82.87, 303.76]

 
Summary of findings for the main comparison. Nutritional advice compared to no counselling or advice during pregnancy for perinatal outcomes

Nutritional advice compared to no counselling or advice during pregnancy for perinatal outcomes

Patient or population: Pregnant women
Settings:
Intervention: Nutritional advice during pregnancy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlNutritional advice during pregnancy

StillbirthStudy populationRR 0.37
(0.07 to 1.9)
431
(1 study)
⊕⊕⊝⊝
low1,2

24 per 10009 per 1000
(2 to 46)

Moderate

24 per 10009 per 1000
(2 to 46)

Neonatal deathStudy populationRR 1.28
(0.35 to 4.72)
448
(1 study)
⊕⊕⊝⊝
low1,2

18 per 100023 per 1000
(6 to 83)

Moderate

18 per 100023 per 1000
(6 to 85)

Birthweight (g)The mean birthweight (g) in the intervention groups was
205.75 higher
(242.54 lower to 654.03 higher)
426
(2 studies)
⊕⊝⊝⊝
very low1,2,3

Birth head circumference (cm)The mean birth head circumference (cm) in the intervention groups was
0.99 higher
(0.43 to 1.55 higher)
389
(1 study)
⊕⊕⊕⊝
moderate2

Small-for-gestational ageStudy populationRR 0.97
(0.45 to 2.11)
404
(1 study)
⊕⊕⊝⊝
low1,2

60 per 100058 per 1000
(27 to 127)

Moderate

60 per 100058 per 1000
(27 to 127)

Preterm birthStudy populationRR 0.46
(0.21 to 0.98)
449
(2 studies)
⊕⊕⊝⊝
low2,3

85 per 100039 per 1000
(18 to 84)

Moderate

92 per 100042 per 1000
(19 to 90)

Protein intake (g/day)The mean protein intake (g/day) in the intervention groups was
6.99 higher
(3.02 to 10.97 higher)
632
(3 studies)
⊕⊕⊝⊝
low2,4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Wide 95% CI.
2 Sample size is smaller than optimal information size.
3 Allocation concealment, blinding, incomplete outcome reporting is high risk of bias in one study.
4 Random sequence, allocation concealment is unclear in some studies.
 
Summary of findings 2. Balanced protein and energy supplementation compared to control or no intervention in pregnancy for perinatal and maternal outcomes

Balanced protein and energy supplementation compared to control or no intervention in pregnancy for perinatal and maternal outcomes

Patient or population: Pregnant women
Settings:
Intervention: Balanced protein/energy supplementation in pregnancy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlBalanced protein/energy supplementation in pregnancy

StillbirthStudy populationRR 0.62
(0.4 to 0.98)
3408
(5 studies)
⊕⊕⊕⊝
moderate1

28 per 100017 per 1000
(11 to 27)

Moderate

25 per 100015 per 1000
(10 to 25)

Neonatal deathStudy populationRR 0.68
(0.43 to 1.07)
3381
(5 studies)
⊕⊕⊝⊝
low1,2

26 per 100018 per 1000
(11 to 28)

Moderate

17 per 100012 per 1000
(7 to 18)

Birthweight (g)The mean birthweight (g) in the intervention groups was
40.96 higher
(4.66 to 77.26 higher)
5385
(11 studies)
⊕⊕⊕⊝
moderate1

Small-for-gestational ageStudy populationRR 0.79
(0.69 to 0.9)
4408
(7 studies)
⊕⊕⊕⊝
moderate1

173 per 1000137 per 1000
(120 to 156)

Moderate

163 per 1000129 per 1000
(112 to 147)

Preterm birthStudy populationRR 0.96
(0.8 to 1.16)
3384
(5 studies)
⊕⊕⊕⊝
moderate3

112 per 1000108 per 1000
(90 to 130)

Moderate

113 per 1000108 per 1000
(90 to 131)

Pre-eclampsiaStudy populationRR 1.48
(0.82 to 2.66)
463
(2 studies)
⊕⊝⊝⊝
very low1,2,4

73 per 1000108 per 1000
(60 to 195)

Moderate

38 per 100056 per 1000
(31 to 101)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Allocation concealment, blinding, incomplete outcome reporting is high risk of bias in some studies.
2 Wide 95% CI.
3 Random sequence, allocation concealment is unclear in some studies.
4 Sample size is smaller than optimal information size.
 
Summary of findings 3. High protein supplementation in pregnancy and perinatal outcomes

High protein supplementation in pregnancy and perinatal outcomes

Patient or population: Pregnant women
Settings:
Intervention: High protein supplementation in pregnancy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlHigh protein supplementation in pregnancy

StillbirthStudy populationRR 0.81
(0.31 to 2.15)
529
(1 study)
⊕⊕⊝⊝
low1,2

33 per 100027 per 1000
(10 to 72)

Moderate

33 per 100027 per 1000
(10 to 71)

Neonatal deathStudy populationRR 2.78
(0.75 to 10.36)
529
(1 study)
⊕⊕⊝⊝
low1,2

11 per 100031 per 1000
(8 to 115)

Moderate

11 per 100031 per 1000
(8 to 114)

Small-for-gestational ageStudy populationRR 1.58
(1.03 to 2.41)
505
(1 study)
⊕⊕⊕⊝
moderate2

117 per 1000185 per 1000
(121 to 282)

Moderate

117 per 1000185 per 1000
(121 to 282)

Birthweight (g)The mean birthweight (g) in the intervention groups was
73 lower
(171.26 lower to 25.26 higher)
504
(1 study)
⊕⊕⊝⊝
low1,2

Preterm birthStudy populationRR 1.14
(0.83 to 1.56)
505
(1 study)
⊕⊕⊝⊝
low1,2

219 per 1000249 per 1000
(182 to 341)

Moderate

219 per 1000250 per 1000
(182 to 342)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Wide 95% CI.
2 Sample size is smaller than optimal information size.
 
Summary of findings 4. Isocaloric balanced protein supplementation in pregnancy and outcomes

Isocaloric balanced protein supplementation in pregnancy and outcomes

Patient or population: Pregnant women
Settings:
Intervention: Isocaloric balanced protein supplementation in pregnancy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlIsocaloric balanced protein supplementation in pregnancy

Birthweight (g)The mean birthweight (g) in the intervention groups was
108.25 higher
(220.89 lower to 437.4 higher)
184
(2 studies)
⊕⊝⊝⊝
very low1,2,3

Weekly gestational weight gain (g/week)The mean weekly gestational weight gain (g/week) in the intervention groups was
110.45 higher
(82.87 lower to 303.76 higher)
184
(2 studies)
⊕⊝⊝⊝
very low1,3,4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Two trials are unclear risk of random sequence generation, allocation concealment, blinding, and selective reporting.
2 I-square is 84%, P value = 0.01.
3 Sample size is smaller than optimal information size.
4 I-square is 85% with P value 0.01.