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Insecticide-treated nets for preventing malaria in pregnancy

  1. Carrol L Gamble1,*,
  2. John Paul Ekwaru2,
  3. Feiko O ter Kuile3

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 12 FEB 2009

DOI: 10.1002/14651858.CD003755.pub2

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Additional Information

How to Cite

Gamble CL, Ekwaru JP, ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003755. DOI: 10.1002/14651858.CD003755.pub2.

Author Information

  1. 1

    University of Liverpool, Centre for Medical Statistics and Health Evaluation, Liverpool, UK

  2. 2

    Uganda Virus Research Institute, Centers for Disease Control and Prevention, Entebbe, Uganda

  3. 3

    Liverpool School of Tropical Medicine, Child & Reproductive Health Group, Liverpool, Merseyside, UK

*Carrol L Gamble, Centre for Medical Statistics and Health Evaluation, University of Liverpool, Shelley's Cottage, Brownlow Street, Liverpool, L69 3GS, UK. c.gamble@liv.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 8 JUL 2009

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Characteristics of included studies [ordered by study ID]
Browne 2001
MethodsCluster randomized controlled trial: 96 clusters, 48 per group

Generation of allocation sequence and allocation concealment: determined by "open ballot of community leaders"

Blinding: open

Inclusion of randomized participants in analysis: 1806/1961 (92%) had blood taken in the third trimester for malaria and haemoglobin outcomes; 847/1961 (43%) had pregnancy outcomes reported
Participants1961 pregnant women (1033 intervention and 928 control) of any parity who had attended the study clinic at least once
Interventions1. ITNs
Insecticide: permethrin (500 g/m2)
Size: rectangular; 4 sizes ranging between 190 cm and 100 cm in width and by 180 cm in length and 150 cm in height

2. No nets
Outcomes1. Malaria infection
2. Antenatal parasitaemia (by parity and season)
3. Antenatal anaemia
4. Low birthweight
5. Mean and standard deviation of birthweight
6. Haemoglobin
7. Placental parasitaemia
8. Stillbirth
NotesLocation: living compounds in Kassena-Nankana district, Ghana

Date: June 1994 to April 1995

Malaria transmission: hyperendemic and perennial with peaks in the rainy season

Trial assessed the impact of ITN use on malaria and anaemia in pregnancy as a supplementary study in a major cluster randomized trial of bed nets supported by WHO/TDR

Active surveillance was used to track all deliveries of the recruited women, but this had to be abandoned in favour of passive surveillance after 6 months because of resource constraints




Browne 2001 G1, dry
MethodsBrowne 2001 results for women in first pregnancy during the dry season
Participants—
Interventions—
Outcomes—
Notes—




Browne 2001 G1, wet
MethodsBrowne 2001 results for women in first pregnancy during the wet season
Participants—
Interventions—
Outcomes—
Notes—




Browne 2001 G2, dry
MethodsBrowne 2001 results for women in second pregnancy during the dry season
Participants—
Interventions—
Outcomes—
Notes—




Browne 2001 G2, wet
MethodsBrowne 2001 results for women in second pregnancy during the wet season
Participants—
Interventions—
Outcomes—
Notes—




Browne 2001 G3+, dry
MethodsBrowne 2001 results for women in third or greater pregnancy during the dry season
Participants—
Interventions—
Outcomes—
Notes—




Browne 2001 G3+, wet
MethodsBrowne 2001 results for in third or greater pregnancy during the wet season
Participants—
Interventions—
Outcomes—
Notes—




Dolan 1993
MethodsIndividual randomized controlled trial

Generation of allocation sequence and allocation concealment: states "randomized", but the methods not described

Blinding: ITNs versus untreated nets comparison double blind (participants, antenatal clinic staff, and supervising physician)

Inclusion of randomized participants in analysis: of 223 enrolled into ITN and untreated groups 203 (91%) completed
ParticipantsPregnant women of all parity

341 women enrolled; 34 were excluded from the analysis because they either delivered within 2 weeks of enrolment or were lost to follow up
Interventions1. ITNs
Insecticide: permethrin (500 g/m2)
Size (cm): 70 wide by 180 long by 150 high
Material: nylon, mesh size 196, denier 70

2. Untreated nets

3. No study nets, but some women in this group had their own family-size untreated nets supplied by the Consortium of Christian Relief Organizations and Interaid

Additional interventions: women with uncomplicated Plasmodium falciparum were treated with quinine sulphate (30 mg salt/kg/d in 3 divided doses for 7 d), and Plasmodium vivax infections with chloroquine (25 mg/kg base over 3 d); severe cases of P. falciparum were treated with intravenous quinine in a local hospital
Outcomes1. Malaria infection during pregnancy
2. Antenatal parasitaemia
3. Illness warranting hospitalization
4. Antenatal anaemia
5. Premature delivery
6. Stillbirth
7. Infant mortality
8. Low birthweight
9. Birthweight
NotesLocation: 3 camps (Shoklo, Bonoklo, and Maesalit) for displaced people of the Karen ethnic minority, Thailand

Date: recruitment between October 1990 and September 1992

Malaria transmission: mesoendemic with estimated attack rates of 1.0/year in the under 10 years age group and 0.8/year in older children and adults

In the published results the 'no study nets group' was split into those who had no nets and those who had received nets from the charity: we felt the validity of the no study nets control group was compromised and decided to use data only on the treated versus untreated nets comparison




Njagi 2002
MethodsIndividual randomized controlled trial

Generation of allocation sequence: enrolled women randomized into the 4 arms in blocks of 12 using computer-generated random numbers; randomization numbers were prepared before the trial started and kept at each recruitment centre until the end of the trial

Allocation concealment: method not described

Blinding: open for ITNs versus no nets comparison; double blind for sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine placebo comparison

Inclusion of randomized participants in analysis: 963 women were recruited, out of which 752 (78%) were followed up to completion
ParticipantsWomen in their first or second pregnancy
Interventions1. ITNs plus sulfadoxine-pyrimethamine
2. ITNs
3. Sulfadoxine-pyrimethamine
4. Placebo

Net size (cm): 190 wide by 180 long by 150 high
Net material: polyester
Outcomes1. Malaria infection
2. Maternal death
3. Antenatal parasitaemia
4. Spontaneous miscarriage
5. Maternal anaemia
6. Haemoglobin
7. Stillbirth
8. Birthweight
NotesLocation: Bondo District Nyanza province, Kenya

Date: July 1997 to September 1999

Malaria transmission: perennial with 2 peaks coinciding with the rainy seasons with 90 to 400 infective bites per person annually




Njagi 2002 +SP
MethodsNjagi 2002 results for ITNs nets plus sulfadoxine-pyrimethamine versus no nets plus sulfadoxine-pyrimethamine
Participants—
Interventions—
Outcomes—
Notes—




Njagi 2002 -SP
MethodsNjagi 2002 results for ITNs plus placebo versus placebo
Participants
Interventions—
Outcomes—
Notes—




Shulman 1998
MethodsCluster randomized controlled trial: 56 clusters (28:28) each of approximately 1000 individuals

Generation of allocation sequence and allocation concealment: determined by "open ballot "; information received via personal communication from Christian Lengeler

Blinding: open

Inclusion of randomized participants in analysis: of 503 recruited 462 (91.8%) had third trimester blood sample, 130 (25.8%) delivered in hospital, and 497 (98.8%) followed up at least 4 weeks after delivery
Participants503 women pregnant for the first time with singleton pregnancies or history of previous pregnancy that did not go beyond 12 weeks
Interventions1. ITNs
Insecticide: permethrin (500 g/m2)
Size (cm): 190 wide by 180 long by 150 high
Material: green

2. No nets

Additional interventions: all women with haemoglobin < 10 g/dL were given haematins and those with a positive slide for malaria were treated with sulfadoxine-pyrimethamine; all women with severe anaemia also given sulfadoxine-pyrimethamine irrespective of the results of their malaria smear, based on the assumption that those with negative smear would be likely to have placental parasitaemia

Sufficient nets provided for all members of randomized households
Outcomes1. Malaria infection
2. Antenatal parasitaemia
3. Antenatal anaemia
4. Haemoglobin
5. Placental parasitaemia
6. Stillbirth
7. Birthweight
8. Perinatal mortality
9. Neonatal mortality
NotesLocation: resident in rural populations Kilifi District, Kenya

Date: September 1994 to November 1995

Malaria transmission: endemic and perennial with peaks in the 2 rainy seasons with individuals on average receiving 10 infective bites per person per year (ranging from 1 every 2 years to nearly 60 per person per year)

The trial recruited pregnant women who came from a rural population that had already been randomized to receiving or not receiving nets treated with permethrin (500 g/m2) as part of a trial assessing the effect of ITNs on childhood mortality and severe malaria in children; randomization and distribution of nets had been finished by August 1993, and this study was conducted between September 1994 and November 1995




ter Kuile 2003
MethodsCluster randomized controlled trial 79 villages: 60 villages described as 'non cohort' with delivery data only, and 19 villages described as 'cohort' with outcomes collected prior to delivery and at delivery

Generation of allocation sequence and allocation concealment: "open lottery"

Blinding: open

Inclusion of randomized participants in analysis: birth outcomes for 2754/2991 (92%); minimum of 764/780 (98%) included in analysis of outcomes assessing the impact of nets during pregnancy
Participants2991 pregnant women of all parity
Interventions1. ITNs
Insecticide: permethrin; pretreated at distribution and re-treated biannually to maintain a target dose of 500 mg/m2
Size: not provided
Note: multiple nets provided to large households according to bed space measurements and baseline demographic data, providing an intervention ITN coverage ratio of 1.5 persons per ITN

2. No nets
Outcomes1. Malaria infection
2. Antenatal parasitaemia
3. Spontaneous miscarriage
4. Maternal anaemia
5. Haemoglobin
6. Premature delivery
7. Stillbirth
8. Birthweight
NotesLocation: Rarieda Division (Asebo), Siaya district, Kenya

Malarial transmission: intense perennial transmission with 60 to 300 infected bites per person annually with peaks in the 3 rainy seasons

Conducted within the context of a large community-based randomized controlled trial designed to assess the impact of ITNs on mortality in children < 5 years of age. The mortality in children trial consisted of two main sites, Asebo and Gem, but the study on the impact of ITNs in pregnancy was conducted in Asebo area only (200 km2). The trial involved randomizing villages to the intervention group, in which all households received ITNs during the fourth quarter of 1996 or control group which received ITNs in April 1999 after the trial was completed




ter Kuile 2003 G1-4
Methodster Kuile 2003 results for women in their first to fourth pregnancy
Participants—
Interventions—
Outcomes—
Notes—




ter kuile 2003 G5+
Methodster Kuile 2003 results for women in their fifth or greater pregnancy
Participants—
Interventions—
Outcomes—
Notes—
 ITN: insecticide-treated net; WHO/TDR: World Health Organization/United Nations Development Programme (UNDP)/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.


 
Characteristics of excluded studies [ordered by study ID]
StudyReason for exclusion
D'Alessandro 19961. Cluster randomized trial that did not adjust for clustering in the analysis
2. Substantial proportions of missing data: of the 651 women in their first pregnancy recruited, only 358 (55%) had blood samples collected at 32 weeks gestation that were used in the analysis; 537 (82%) were available for the pregnancy outcomes but only 380 (58%) were available for birthweight with 289 (44%) available with placenta biopsy; 319 (49%) had information on survival


 
Comparison 1. Insecticide-treated nets versus no nets
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Severe anaemia4Various (Fixed, 95% CI)Subtotals only
    1.1 Odds ratio (third trimester)
2Various (Fixed, 95% CI)0.77 [0.56, 1.08]
    1.2 Risk ratio (at delivery)
2Various (Fixed, 95% CI)0.98 [0.63, 1.52]
    1.3 Hazard ratio
2Various (Fixed, 95% CI)0.89 [0.61, 1.31]
 2 Any anaemia5Various (Random, 95% CI)Subtotals only
    2.1 Odds ratio (third trimester)
1Various (Random, 95% CI)0.88 [0.71, 1.10]
    2.2 Odds ratio (at delivery)
2Various (Random, 95% CI)0.95 [0.50, 1.79]
    2.3 Hazard ratio
2Various (Random, 95% CI)0.90 [0.71, 1.13]
 3 Haemoglobin (g/L)11Mean difference (Random, 95% CI)Subtotals only
    3.1 Third trimester: first or second pregnancy
5Mean difference (Random, 95% CI)-0.04 [-2.41, 2.33]
    3.2 Third trimester: third or greater pregnancy
3Mean difference (Random, 95% CI)0.30 [-3.38, 3.97]
    3.3 At delivery: first or second pregnancy
3Mean difference (Random, 95% CI)1.95 [-2.61, 6.51]
 4 Low birthweight4Various (Fixed, 95% CI)0.80 [0.64, 1.00]
    4.1 Risk ratio: first or second pregnancy
3Various (Fixed, 95% CI)0.77 [0.61, 0.98]
    4.2 Risk ratio: fifth or greater pregnancy
1Various (Fixed, 95% CI)1.12 [0.56, 2.24]
 5 Birthweight (kg)10Mean difference (Fixed, 95% CI)0.06 [0.02, 0.09]
    5.1 First or second pregnancy
8Mean difference (Fixed, 95% CI)0.05 [0.02, 0.09]
    5.2 Third or greater pregnancy
2Mean difference (Fixed, 95% CI)0.08 [-0.13, 0.28]
 6 Clinical malaria illness during pregnancy2Various (Fixed, 95% CI)Totals not selected
    6.1 Odds ratio
1Various (Fixed, 95% CI)Not estimable
    6.2 Hazard ratio
1Various (Fixed, 95% CI)Not estimable
 7 Peripheral parasitaemia6Various (Fixed, 95% CI)Subtotals only
    7.1 Odds ratio: third trimester
2Various (Fixed, 95% CI)0.88 [0.73, 1.06]
    7.2 Risk ratio: at delivery
4Various (Fixed, 95% CI)0.76 [0.67, 0.86]
    7.3 Hazard ratio
2Various (Fixed, 95% CI)0.67 [0.52, 0.86]
 8 Parasite density8Geometric mean ratio (Fixed, 95% CI)0.93 [0.77, 1.11]
    8.1 First or second pregnancy
6Geometric mean ratio (Fixed, 95% CI)0.82 [0.66, 1.02]
    8.2 Third or greater pregnancy
2Geometric mean ratio (Fixed, 95% CI)1.28 [0.90, 1.82]
 9 Placental parasitaemia5Risk Ratio (Random, 95% CI)0.79 [0.63, 0.98]
    9.1 First or second pregnancy
4Risk Ratio (Random, 95% CI)0.82 [0.61, 1.11]
    9.2 Fifth or greater pregnancy
1Risk Ratio (Random, 95% CI)0.72 [0.48, 1.08]
 10 Fetal loss5Risk Ratio (Fixed, 95% CI)0.68 [0.48, 0.98]
    10.1 First or second pregnancy
4Risk Ratio (Fixed, 95% CI)0.67 [0.47, 0.97]
    10.2 Fifth or greater pregnancy
1Risk Ratio (Fixed, 95% CI)1.02 [0.17, 6.23]
 
Table 1. Detailed search strategies
Search setCIDG SRaCENTRALMEDLINEbEMBASEbLILACSb
1malariamalariamalariamalariamalaria
2pregnan*pregnan*pregnan*pregnan*pregnan*
3womanwomanwomanwomanwoman
4womenwomenwomenwomenwomen
53 or 43 or 43 or 43 or 43 or 4
61 and 2 and 51 and 2 and 51 and 2 and 51 and 2 and 51 and 2 and 5
7net*net*net*net*net*
8ITN*ITN*ITN*ITN*6 and 7
9ITM*ITM*ITM*ITM*—
107 or 8 or 97 or 8 or 97 or 8 or 97 or 8 or 9—
116 and 106 and 106 and 106 and 10—
 aCochrane Infectious Diseases Group Specialized Register.
bSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Higgins 2005); upper case: MeSH or EMTREE heading; lower case: free text term.
 
Table 2. Risk of bias assessmenta
TrialGeneration of allocation sequenceAllocation concealmentBlindingInclusion of all randomized participants in the analysis
Dolan 1993Method not describedNot describedDouble blind (participants, antenatal clinic staff, and supervising physician) for ITNs versus untreated nets comparisonAdequate
Shulman 1998AdequateAdequateOpenAdequate for number with a third trimester blood sample

Inadequate for number women who delivered in hospital

Adequate for number followed up at least 4 weeks after delivery

Adequate for number with a third trimester blood sample

Inadequate for number women who delivered in hospital

Adequate for number followed up at least 4 weeks after delivery
Browne 2001AdequateAdequateOpenAdequate for number with blood taken in third trimester for malaria and haemoglobin

Inadequate for number with pregnancy outcomes reported
Njagi 2002AdequateNot describedOpen for ITNs versus no nets comparison

Double blind for sulfadoxine-pyrimethamine (SP) versus SP placebo comparison

Open for ITNs versus no nets comparison

Double blind for sulfadoxine-pyrimethamine (SP) versus SP placebo comparison		Inadequate for number evaluated at delivery
ter Kuile 2003AdequateAdequateOpenAdequate number for birth outcomes and analysis of outcomes assessing the impact of nets during pregnancy
 aDetails of methods used in individual trials are in the 'Characteristics of included studies'.
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