Insecticide‐treated nets for preventing malaria in pregnancy

Carrol L Gamble; John Paul Ekwaru; Feiko O ter Kuile

doi:10.1002/14651858.CD003755.pub2

Mosquiteros tratados con insecticida para la prevención del paludismo en el embarazo

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Referencias

References to studies included in this review

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estudios excluidos
otras referencias

Binka FN, Adongo P. Acceptability and use of insecticide impregnated bednets in northern Ghana. Tropical Medicine and International Health 1997;2(5):499‐507.

Binka FN, Kubaje A, Adjuik M, Williams LA, Lengeler C, Maude GH, et al. Impact of permethrin impregnated bednets on child mortality in Kassena‐Nankana district, Ghana: a randomized controlled trial. Tropical Medicine and International Health 1996;1(2):147‐54.

Browne EN, Maude GH, Binka FN. The impact of insecticide‐treated bednets on malaria and anaemia in pregnancy in Kassena‐Nankana district, Ghana: a randomized controlled trial. Tropical Medicine and International Health 2001;6(9):667‐76.

Browne 2001 results for women in first pregnancy during the dry season.

Browne 2001 results for women in first pregnancy during the wet season.

Browne 2001 results for women in second pregnancy during the dry season.

Browne 2001 results for women in second pregnancy during the wet season.

Browne 2001 results for women in third or greater pregnancy during the dry season.

Browne 2001 results for in third or greater pregnancy during the wet season.

Dolan G, ter Kuile FO, Jacoutot V, White NJ, Luxemburger C, Malankirii L, et al. Bed nets for the prevention of malaria and anaemia in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene 1993;87(6):620‐6.

Njagi JK. The effects of sulfadoxine‐pyrimethamine intermittent treatment and pyrethroid impregnanted bed nets on malaria morbidity in pregnancy and birth weight in Bondo District, Kenya [PhD thesis]. Nairobi: University of Nairobi, 2002.

Njagi JK, Magnussen P, Estambale B, Ouma J, Mugo B. Prevention of anaemia in pregnancy using insecticide‐treated bednets and sulfadoxine‐pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 2003;97(3):277‐82.

Njagi 2002 results for ITNs nets plus sulfadoxine‐pyrimethamine versus sulfadoxine‐pyrimethamine versus (3) sulfadoxine‐pyrimethamine.

Njagi 2002 results for ITNs versus placebo.

Nevill CG, Some ES, Mung'ala VO, Mutemi M, New L, Marsh K, et al. Insecticide‐treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Tropical Medicine and International Health 1996;1(2):139‐46.

Shulman C. Malaria and anaemia in pregnancy: importance, detection and prevention [PhD thesis]. Amsterdam: University of Amsterdam, 2001.

Shulman CE, Dorman EK, Talisuna AO, Lowe BS, Nevill C, Snow RW, et al. A community randomized controlled trial of insecticide‐treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast. Tropical Medicine and International Health 1998;3(3):197‐204.

Phillips‐Howard PA, Nahlen BL, Alaii JA, ter Kuile F, Gimnig JE, Terlouw DJ, et al. The efficacy of permethrin‐treated bed nets on child mortality and morbidity in western Kenya I. Development of infrastructure and description of study site. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:3‐9.

Phillips‐Howard PA, Nahlen BL, Kolczak MS, Hightower AW, ter Kuile FO, Alaii JA, et al. Efficacy of permethrin‐treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:23‐9.

Phillips‐Howard PA, ter Kuile FO, Nahlen BL, Alaii JA, Gimnig JE, Kolczak MS, et al. The efficacy of permethrin‐treated bed nets on child mortality and morbidity in western Kenya II. Study design and methods. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:10‐5.

ter Kuile FO, Terlouw DJ, Phillips‐Howard PA, Hawley WA, Friedman JF, Kariuki SK, et al. Reduction of malaria during pregnancy by permethrin‐treated bed nets in an area of intense perennial malaria transmission in western Kenya. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:50‐60.

ter Kuile 2003 results for women in their first to third pregnancy.

ter Kuile 2003 results for women in their fourth or greater pregnancy.

References to studies excluded from this review

Ir a:

estudios incluidos
otras referencias

D'Alessandro U, Langerock P, Bennett S, Francis N, Cham K, Greenwood BM, et al. The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia. Transactions of the Royal Society of Tropical Medicine and Hygiene 1996;90(5):487‐92.

D'Alessandro U, Olaleye BO, McGuire W, Langerock P, Bennett S, Aikins MK, et al. Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme. Lancet 1995;345(8948):479‐83.

Additional references

Ir a:

estudios incluidos
estudios excluidos

Binka FN, Kubaje A, Adjuik M, Williams LA, Lengeler C, Maude GH, et al. Impact of permethrin impregnated bednets on child mortality in Kassena‐Nankana district, Ghana: a randomized controlled trial. Tropical Medicine and International Health 1996;1(2):147‐54.

Brabin BJ. An analysis of malaria in pregnancy in Africa. Bulletin of the World Health Organization 1983;61(6):1005‐16.

Deeks JJ, Altman DG. Effect measures for meta‐analysis of trials with binary outcome data. In: Egger M, Davey Smith G, Altman DG editor(s). Systematic reviews in health care. Meta‐analysis in context. 2nd Edition. BMJ Books, 2001:320.

Deeks JJ. Swots Corner: What is an odds ratio?. www.jr2.ox.ac.uk/bandolier/band25/b25‐6.html (accessed 9 November 2005).

Garner P, Gülmezoglu AM. Drugs for preventing malaria‐related illness in pregnant women and death in the newborn. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD000169]

Guyatt HL, Snow RW. The epidemiology and burden of Plasmodium falciparum‐related anemia among pregnant women in sub‐Saharan Africa. American Journal of Tropical Medicine and Hygiene 2001;64 Suppl 1‐2:36‐44.

Guyatt HL, Snow RW. Malaria in pregnancy as an indirect cause of infant mortality in sub‐Saharan Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 2001;95(6):569‐76.

Hawley WA, Phillips‐Howard PA, ter Kuile FO, Terlouw DJ, Vulule JM, Ombok M, et al. Community‐wide effects of permethrin‐treated bednets on child mortality and malaria morbidity in western Kenya. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:121‐7.

Google Scholar

Higgins J, Green S, editors. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]; Appendix 5b. www.cochrane.org/resources/handbook/hbook.htm (accessed 1 October 2005).

Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6.

Kerry AM, Bland JM. Statistical notes. Analysis of trial randomised in clusters. BMJ 1998;316:54.

Lengeler C. Insecticide‐treated bed nets and curtains for preventing malaria. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD000363.pub2]

Lindsay S, Ansell J, Selman C, Cox V, Hamilton K, Walraven G, et al. Effect of pregnancy on exposure to malaria mosquitoes. Lancet 2000;335(9219):1972.

Marchant T, Schellenberg JA, Edgar T, Nathan R, Abdulla S, Mukasa O, et al. Socially marketed insecticide‐treated nets improve malaria and anaemia in pregnancy in southern Tanzania. Tropical Medicine and International Health 2002;7(2):149‐58.

Nevill CG, Some ES, Mung'ala VO, Mutemi M, New L, Marsh K, et al. Insecticide‐treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Tropical Medicine and International Health 1996;1(2):139‐46.

Nosten F, Rogerson SJ, Beeson JG, McGready R, Mutabingwa TK, Brabin B. Malaria in pregnancy and the endemicity spectrum: what can we learn?. Trends in Parasitology 2004;20(9):425‐32.

Phillips‐Howard PA, Nahlen BL, Kolczak MS, Hightower AW, ter Kuile FO, Alaii JA, et al. Efficacy of permethrin‐treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya. American Journal of Tropical Medicine and Hygiene 2003;68 Suppl 4:23‐9.

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.

Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria‐endemic areas. American Journal of Tropical Medicine and Hygiene 2001;64 Suppl 1‐2:28‐35.

van Geertruyden JP, Thomas F, Erhart A, D'Alessandro U. The contribution of malaria in pregnancy to perinatal mortality. American Journal of Tropical Medicine and Hygiene 2004;71 Suppl 2:35‐40.

World Health Organization. The African summit on Roll Back Malaria. mosquito.who.int/docs/abuja_declaration.pdf (accessed 21 November 2001).

World Health Organization ‐ Regional Office for Africa. A strategic framework for malaria prevention and control during pregnancy in the African region. Brazzaville: World Health Organization, 2004.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Browne 2001

Methods	Cluster 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
Participants	1961 pregnant women (1033 intervention and 928 control) of any parity who had attended the study clinic at least once
Interventions	1. 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
Outcomes	1. 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
Notes	Location: 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

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

Browne 2001 G1, wet

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

Browne 2001 G2, dry

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

Browne 2001 G2, wet

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

Browne 2001 G3+, dry

Methods	Browne 2001 results for women in third or greater pregnancy during the dry season
Participants	—
Interventions	—
Outcomes	—
Notes	—

Browne 2001 G3+, wet

Methods	Browne 2001 results for in third or greater pregnancy during the wet season
Participants	—
Interventions	—
Outcomes	—
Notes	—

Dolan 1993

Methods	Individual 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
Participants	Pregnant 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
Interventions	1. 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
Outcomes	1. 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
Notes	Location: 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

Methods	Individual 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
Participants	Women in their first or second pregnancy
Interventions	1. 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
Outcomes	1. Malaria infection 2. Maternal death 3. Antenatal parasitaemia 4. Spontaneous miscarriage 5. Maternal anaemia 6. Haemoglobin 7. Stillbirth 8. Birthweight
Notes	Location: 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

Methods	Njagi 2002 results for ITNs nets plus sulfadoxine‐pyrimethamine versus no nets plus sulfadoxine‐pyrimethamine
Participants	—
Interventions	—
Outcomes	—
Notes	—

Njagi 2002 ‐SP

Methods	Njagi 2002 results for ITNs plus placebo versus placebo
Participants
Interventions	—
Outcomes	—
Notes	—

Shulman 1998

Methods	Cluster 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
Participants	503 women pregnant for the first time with singleton pregnancies or history of previous pregnancy that did not go beyond 12 weeks
Interventions	1. 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
Outcomes	1. Malaria infection 2. Antenatal parasitaemia 3. Antenatal anaemia 4. Haemoglobin 5. Placental parasitaemia 6. Stillbirth 7. Birthweight 8. Perinatal mortality 9. Neonatal mortality
Notes	Location: 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

Methods	Cluster 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
Participants	2991 pregnant women of all parity
Interventions	1. 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
Outcomes	1. Malaria infection 2. Antenatal parasitaemia 3. Spontaneous miscarriage 4. Maternal anaemia 5. Haemoglobin 6. Premature delivery 7. Stillbirth 8. Birthweight
Notes	Location: 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

Methods	ter Kuile 2003 results for women in their first to fourth pregnancy
Participants	—
Interventions	—
Outcomes	—
Notes	—

ter kuile 2003 G5+

Methods	ter 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]

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estudios incluidos

Study

Reason for exclusion

D'Alessandro 1996

1. 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

Data and analyses

Open in table viewer

Comparison 1. Insecticide‐treated nets versus no nets

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe anaemia Show forest plot	4		Various (Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 1 Severe anaemia.
1.1 Odds ratio (third trimester)	2		Various (Fixed, 95% CI)	0.77 [0.56, 1.08]
1.2 Risk ratio (at delivery)	2		Various (Fixed, 95% CI)	0.98 [0.63, 1.52]
1.3 Hazard ratio	2		Various (Fixed, 95% CI)	0.89 [0.61, 1.31]
2 Any anaemia Show forest plot	5		Various (Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.2 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 2 Any anaemia.
2.1 Odds ratio (third trimester)	1		Various (Random, 95% CI)	0.88 [0.71, 1.10]
2.2 Odds ratio (at delivery)	2		Various (Random, 95% CI)	0.95 [0.50, 1.79]
2.3 Hazard ratio	2		Various (Random, 95% CI)	0.90 [0.71, 1.13]
3 Haemoglobin (g/L) Show forest plot	11		Mean difference (Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 3 Haemoglobin (g/L).
3.1 Third trimester: first or second pregnancy	5		Mean difference (Random, 95% CI)	‐0.04 [‐2.41, 2.33]
3.2 Third trimester: third or greater pregnancy	3		Mean difference (Random, 95% CI)	0.30 [‐3.38, 3.97]
3.3 At delivery: first or second pregnancy	3		Mean difference (Random, 95% CI)	1.95 [‐2.61, 6.51]
4 Low birthweight Show forest plot	4		Various (Fixed, 95% CI)	0.80 [0.64, 1.00]
Open in figure viewer Analysis 1.4 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 4 Low birthweight.
4.1 Risk ratio: first or second pregnancy	3		Various (Fixed, 95% CI)	0.77 [0.61, 0.98]
4.2 Risk ratio: fifth or greater pregnancy	1		Various (Fixed, 95% CI)	1.12 [0.56, 2.24]
5 Birthweight (kg) Show forest plot	10		Mean difference (Fixed, 95% CI)	0.06 [0.02, 0.09]
Open in figure viewer Analysis 1.5 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 5 Birthweight (kg).
5.1 First or second pregnancy	8		Mean difference (Fixed, 95% CI)	0.05 [0.02, 0.09]
5.2 Third or greater pregnancy	2		Mean difference (Fixed, 95% CI)	0.08 [‐0.13, 0.28]
6 Clinical malaria illness during pregnancy Show forest plot	2		Various (Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.6 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 6 Clinical malaria illness during pregnancy.
6.1 Odds ratio	1		Various (Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Hazard ratio	1		Various (Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Peripheral parasitaemia Show forest plot	6		Various (Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 7 Peripheral parasitaemia.
7.1 Odds ratio: third trimester	2		Various (Fixed, 95% CI)	0.88 [0.73, 1.06]
7.2 Risk ratio: at delivery	4		Various (Fixed, 95% CI)	0.76 [0.67, 0.86]
7.3 Hazard ratio	2		Various (Fixed, 95% CI)	0.67 [0.52, 0.86]
8 Parasite density Show forest plot	8		Geometric mean ratio (Fixed, 95% CI)	0.93 [0.77, 1.11]
Open in figure viewer Analysis 1.8 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 8 Parasite density.
8.1 First or second pregnancy	6		Geometric mean ratio (Fixed, 95% CI)	0.82 [0.66, 1.02]
8.2 Third or greater pregnancy	2		Geometric mean ratio (Fixed, 95% CI)	1.28 [0.90, 1.82]
9 Placental parasitaemia Show forest plot	5		Risk Ratio (Random, 95% CI)	0.79 [0.63, 0.98]
Open in figure viewer Analysis 1.9 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 9 Placental parasitaemia.
9.1 First or second pregnancy	4		Risk Ratio (Random, 95% CI)	0.82 [0.61, 1.11]
9.2 Fifth or greater pregnancy	1		Risk Ratio (Random, 95% CI)	0.72 [0.48, 1.08]
10 Fetal loss Show forest plot	5		Risk Ratio (Fixed, 95% CI)	0.68 [0.48, 0.98]
Open in figure viewer Analysis 1.10 Comparison 1 Insecticide‐treated nets versus no nets, Outcome 10 Fetal loss.
10.1 First or second pregnancy	4		Risk Ratio (Fixed, 95% CI)	0.67 [0.47, 0.97]
10.2 Fifth or greater pregnancy	1		Risk Ratio (Fixed, 95% CI)	1.02 [0.17, 6.23]

Analysis 1.1

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 1 Severe anaemia.

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Analysis 1.2

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 2 Any anaemia.

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Analysis 1.3

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 3 Haemoglobin (g/L).

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Analysis 1.4

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 4 Low birthweight.

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Analysis 1.5

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 5 Birthweight (kg).

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Analysis 1.6

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 6 Clinical malaria illness during pregnancy.

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Analysis 1.7

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 7 Peripheral parasitaemia.

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Analysis 1.8

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 8 Parasite density.

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Analysis 1.9

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 9 Placental parasitaemia.

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Analysis 1.10

Comparison 1 Insecticide‐treated nets versus no nets, Outcome 10 Fetal loss.

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Table 1. Detailed search strategies

Search set	CIDG SR^a	CENTRAL	MEDLINE^b	EMBASE^b	LILACS^b
1	malaria	malaria	malaria	malaria	malaria
2	pregnan*	pregnan*	pregnan*	pregnan*	pregnan*
3	woman	woman	woman	woman	woman
4	women	women	women	women	women
5	3 or 4	3 or 4	3 or 4	3 or 4	3 or 4
6	1 and 2 and 5	1 and 2 and 5	1 and 2 and 5	1 and 2 and 5	1 and 2 and 5
7	net*	net*	net*	net*	net*
8	ITN*	ITN*	ITN*	ITN*	6 and 7
9	ITM*	ITM*	ITM*	ITM*	—
10	7 or 8 or 9	7 or 8 or 9	7 or 8 or 9	7 or 8 or 9	—
11	6 and 10	6 and 10	6 and 10	6 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 1. Detailed search strategies

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Table 2. Risk of bias assessmenta

Trial	Generation of allocation sequence	Allocation concealment	Blinding	Inclusion of all randomized participants in the analysis
Dolan 1993	Method not described	Not described	Double blind (participants, antenatal clinic staff, and supervising physician) for ITNs versus untreated nets comparison	Adequate
Shulman 1998	Adequate	Adequate	Open	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 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 2001	Adequate	Adequate	Open	Adequate for number with blood taken in third trimester for malaria and haemoglobin Inadequate for number with pregnancy outcomes reported
Njagi 2002	Adequate	Not described	Open 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 2003	Adequate	Adequate	Open	Adequate 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'.

Table 2. Risk of bias assessmenta

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Comparison 1. Insecticide‐treated nets versus no nets

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe anaemia Show forest plot	4		Various (Fixed, 95% CI)	Subtotals only

1.1 Odds ratio (third trimester)	2		Various (Fixed, 95% CI)	0.77 [0.56, 1.08]
1.2 Risk ratio (at delivery)	2		Various (Fixed, 95% CI)	0.98 [0.63, 1.52]
1.3 Hazard ratio	2		Various (Fixed, 95% CI)	0.89 [0.61, 1.31]
2 Any anaemia Show forest plot	5		Various (Random, 95% CI)	Subtotals only

2.1 Odds ratio (third trimester)	1		Various (Random, 95% CI)	0.88 [0.71, 1.10]
2.2 Odds ratio (at delivery)	2		Various (Random, 95% CI)	0.95 [0.50, 1.79]
2.3 Hazard ratio	2		Various (Random, 95% CI)	0.90 [0.71, 1.13]
3 Haemoglobin (g/L) Show forest plot	11		Mean difference (Random, 95% CI)	Subtotals only

3.1 Third trimester: first or second pregnancy	5		Mean difference (Random, 95% CI)	‐0.04 [‐2.41, 2.33]
3.2 Third trimester: third or greater pregnancy	3		Mean difference (Random, 95% CI)	0.30 [‐3.38, 3.97]
3.3 At delivery: first or second pregnancy	3		Mean difference (Random, 95% CI)	1.95 [‐2.61, 6.51]
4 Low birthweight Show forest plot	4		Various (Fixed, 95% CI)	0.80 [0.64, 1.00]

4.1 Risk ratio: first or second pregnancy	3		Various (Fixed, 95% CI)	0.77 [0.61, 0.98]
4.2 Risk ratio: fifth or greater pregnancy	1		Various (Fixed, 95% CI)	1.12 [0.56, 2.24]
5 Birthweight (kg) Show forest plot	10		Mean difference (Fixed, 95% CI)	0.06 [0.02, 0.09]

5.1 First or second pregnancy	8		Mean difference (Fixed, 95% CI)	0.05 [0.02, 0.09]
5.2 Third or greater pregnancy	2		Mean difference (Fixed, 95% CI)	0.08 [‐0.13, 0.28]
6 Clinical malaria illness during pregnancy Show forest plot	2		Various (Fixed, 95% CI)	Totals not selected

6.1 Odds ratio	1		Various (Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Hazard ratio	1		Various (Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Peripheral parasitaemia Show forest plot	6		Various (Fixed, 95% CI)	Subtotals only

7.1 Odds ratio: third trimester	2		Various (Fixed, 95% CI)	0.88 [0.73, 1.06]
7.2 Risk ratio: at delivery	4		Various (Fixed, 95% CI)	0.76 [0.67, 0.86]
7.3 Hazard ratio	2		Various (Fixed, 95% CI)	0.67 [0.52, 0.86]
8 Parasite density Show forest plot	8		Geometric mean ratio (Fixed, 95% CI)	0.93 [0.77, 1.11]

8.1 First or second pregnancy	6		Geometric mean ratio (Fixed, 95% CI)	0.82 [0.66, 1.02]
8.2 Third or greater pregnancy	2		Geometric mean ratio (Fixed, 95% CI)	1.28 [0.90, 1.82]
9 Placental parasitaemia Show forest plot	5		Risk Ratio (Random, 95% CI)	0.79 [0.63, 0.98]

9.1 First or second pregnancy	4		Risk Ratio (Random, 95% CI)	0.82 [0.61, 1.11]
9.2 Fifth or greater pregnancy	1		Risk Ratio (Random, 95% CI)	0.72 [0.48, 1.08]
10 Fetal loss Show forest plot	5		Risk Ratio (Fixed, 95% CI)	0.68 [0.48, 0.98]

10.1 First or second pregnancy	4		Risk Ratio (Fixed, 95% CI)	0.67 [0.47, 0.97]
10.2 Fifth or greater pregnancy	1		Risk Ratio (Fixed, 95% CI)	1.02 [0.17, 6.23]

Comparison 1. Insecticide‐treated nets versus no nets

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Referencias

References to studies included in this review

Browne 2001 {published data only}

Browne 2001 G1, dry {published data only}

Browne 2001 G1, wet {published data only}

Browne 2001 G2, dry {published data only}

Browne 2001 G2, wet {published data only}

Browne 2001 G3+, dry {published data only}

Browne 2001 G3+, wet {published data only}

Dolan 1993 {published data only}

Njagi 2002 {published and unpublished data}

Njagi 2002 +SP {published and unpublished data}

Njagi 2002 ‐SP {published and unpublished data}

Shulman 1998 {published data only}

ter Kuile 2003 {published data only}

ter Kuile 2003 G1‐4 {published data only}

ter kuile 2003 G5+ {published data only}

References to studies excluded from this review

D'Alessandro 1996 {published data only}

Additional references

Binka 1996

Brabin 1983

Deeks 2001

Deeks 2005

Garner 2002

Guyatt 2001a

Guyatt 2001b

Hawley 2003

Higgins 2005

Jüni 2001

Kerry 1998

Lengeler 2004

Lindsay 2000

Marchant 2002

Nevill 1996

Nosten 2004

Phillips‐Howard 2003

Review Manager 5 [Computer program]

Steketee 2001

van Geertruyden 2004

WHO 2000

WHO/AFRO 2004

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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