Table 1.
Characteristics of the 16 included studies which contributed estimates to the systematic review
| Author, year | Region, country | Enrolment period | Endemicitya | Study design (n) | Gravidity; % PG | Mean (SD) ageb | IPTp use | Antibody responses included in reviewc | Time of antibody measurement | Clinical outcomesd |
|---|---|---|---|---|---|---|---|---|---|---|
| Aitken, 2010 [51] | Lungwena, Malawi | 2003–2006 | High | RCT (549)e | All; 23.9 | 24.9 (6.7) | Women randomized to standard 2 dose SP or monthly SP | pRBC: CS2 | T2; T3f | LBW, PI, PTB, Anaemiag |
| Babakhanyan, 2014 [52] | Yaounde, Cameroon | 1996–2001 | Intermediate | CC (464)h | MG | PM+ 28 (5); PM− 30 (6) | 76.3% took chemoprophylaxis | VAR2CSA: 1D1-1D2a, FV2 | Delivery | PM, LBW, PI |
| Beeson, 2004 [53] | Blantyre, Malawi | 1998–2000 | Intermediate | CC (181)i | All; 55 | PM+ 20.9; PM- 21.5 | SP | pRBC: CS2 (total IgG, agglutination, CSA adhesion inhibition) | Delivery | PM |
| Chandrasiri, 2014 [54] | Central and southern regions, Sudan | 2010 | Low | CC (121)j | All; 33 | median (IQR) 28 (24, 32) | None reported | pRBC: CS2, VAR2CSA: DBL5ε | T2/T3 | SM |
| Cox, 2005 [55] | Brong Ahafo, Ghana | 2001 | High | RCT (101)k | PG | 21.1 (2.9) | CQ at enrolment | pRBC: FCR3 | T1/T2 and T2/T3 | PM, PI |
| Duffy, 2003 [56] | Kisumu, Kenya | 1995–1997 | High | CS (168) | All; 28 | 23.5 (5.3) | None reported | pRBC: Kenyan placental isolate (CSA adhesion inhibition) | Delivery | PM, LBW, PTB, anaemiag |
| Fowkes, 2012 [57] | Maela, Thailand | 1998–2000 | Low | nCC (467)l | All; Case 22.1, control 15.7 | Cases: median (IQR) 24.5 (20–30.5); Controls: 26 (21–31) | Pregnant women were randomized to CQ or placebo for P. vivax chemoprophylaxis | VAR2CSA DBL5ε | T1 | PI |
| Fried, 2018 [42] | Ouelessebougou, Mali | 2010–2013 | Intermediate | cohort (657) | All; 25.8 | 24.1 (6.4) | SP | VAR2CSA: ID1-ID2a, DBL2, DBL3, DBL3–4, DBL4, DBL5 | T1/T2/T3 and deliverym | PM, LBW, PTB, PI |
| Gnidehou, 2014 [58] | Cordoba, Colombia | DNS | Low | CC (55)n | All; 16 | 21 (6) | No | VAR2CSA: DBL5ε, DBL3X, ID1-ID2 | T2/T3/delivery | PI |
| Guitard, 2008 [59] | Thiadiaye, Senegal | 2001 | Low | cohort (261) | Allo; 22.3 | 24.1 (6.1) | No | VAR2CSA DBL5ε | T1/T2 and delivery | PM |
| Lloyd, 2018 [60] | Yaounde, Cameroon | 1995–2001 | Intermediate | CC (1377)p | All; 35.7 | 25.8 (5.9) | No | VAR2CSA: FV2 | Delivery | Anaemiaq, PM, PTB, and LBW. |
| McLean, 2017 [63] | Madang, PNG | 2005–2007 | Low | CS from cohort (204) | All; 43.2 | median (IQR) 24 (21–28) | Chloroquine prophylaxis | VAR2CSA: DBL5r | Delivery | PM |
| Megnekou, 2005 [43] | Etoa and Yaounde, Cameroon | 1996–1998 | Etoa: High; Yaounde: Intermediate | Cohort (Etoa 29; Yaounde 186) | All; Yaounde 47, Etoa 48 | Yaounde range 15–40; Etoa range 14–38 | < 40% used chemoprophylaxis | pRBC: FCR3 | T1/T2, T2/T3s | PI |
| Staalsoe, 2001 [35] | Ebolowa and Yaounde, Cameroon | 1992–1996 | Ebolowa: High; Yaounde: Intermediate | Ebolowa: CS (113); Yaounde: CS (45); |
Ebolowa: All; 48.7 Yaounde: SG/MG |
DNS | Some chemoprophylaxis | pRBC: Palo Alto | Delivery | PM |
| Staalsoe, 2004 [61] | Kilifi, Kenya | 1996–1997 | Intermediate | CS (477)t | All; 22.2 | Range 14–35+ | No | pRBC: EJ24 | Delivery | PMu, PI, SAv, LBW |
| Teo, 2014 [62] | Blantyre, Malawi | 1999–2006 | Intermediate | Malawi: CS (332) | SG/MG | Median (IQR) 25 (21–27) | SP | pRBC: CS2, VAR2CSA DBL5Ɛ | Delivery | LBWw |
Abbreviations: CC case control, CS cross sectional, LBW low birthweight, MG multigravidae, PI peripheral infection, PM placental malaria, PG primigravidae PTB preterm birth, SA severe anaemia, SG secundigravidae, SM severe malaria, T1 first trimester, T2 second trimester, T3 third trimester
aEndemicity as reported in original paper, in paper referenced in original paper, or as estimated for the latitude and longitude of study site and first year of enrolment using data from Malaria Atlas Project (P. falciparum parasite rate in 2–10 year olds globally, 2000–2017). If study was conducted before 2000 and information on endemicity was not provided in the paper, then the P. f. PR2–10 for the year 2000 was used
bAge is presented as mean (SD) except where indicated
cThis table includes only those Ab responses that met the inclusion criteria of the review. In some studies, additional Ab responses, Ab measurement time points, and subclass responses were reported in the original paper. Unless indicated otherwise, estimates for total IgG responses were included. Details of antigens are included in Additional file 6
dHerein we tabulate only those outcomes that met the inclusion criteria of this review and were available in categorical format (positive or negative for outcome)
eStudy population was a subset of women randomly selected from the Lungwena Antenatal Intervention Study (LAIS) cohort in which women received IPTp (sulfadoxine-pyramethamine) on at least 2 occasions and some women also received two doses of azithromycin on two occasions
fWomen were enrolled at 14–26 week gestation (T2); Antibodies were also measured at 28–34 week gestation (T3) and at 1, 3, and 6 months postpartum
gAnaemia was defined as haemoglobin < 110 g/l
hSamples were originally from a cross-sectional study (total 1944 samples): All samples from PM+ women (n = 116) and 348 randomly selected samples from PM− women were selected from women who had ≥ 3 pregnancies, were ≥ 20 years of age, and had term or premature deliveries. Authors reported that all PM− women had been exposed to malaria since they had Ab to DBL5
iInfected women were individually matched by gravidity, age (± 2 years), and date of delivery (± 2 months) to women without evidence of current or previous placental infection according to the results of placental histological analysis and placental, peripheral, and cord blood smears, and/or to women with evidence of past placental infection (malaria pigment present by placental histological analysis but no parasites seen, together with negative placental, peripheral, and cord blood smears)
jPregnant women who were blood film positive and diagnosed with one or more of the following clinical manifestations were categorized as having SM (n = 39): severe anaemia, haemoglobin levels < 7 g/dL; cerebral malaria, unrousable coma; hypoglycaemia, blood glucose levels < 40 mg/dL; hypotension, systolic blood pressure < 90 mmHg; jaundice, physical diagnosis or bilirubin levels > 3 mg/dL and hyperparasitaemia, > 10,000 parasites/μl. Pregnant women who were parasitaemic without these features were defined as uncomplicated malaria (UM; n = 41). An additional 41 pregnant women with negative blood films and no signs of clinical malaria were enrolled as uninfected controls. Estimates included in this review used uninfected women as the comparator group
kTrial of maternal vitamin A supplementation
lParticipants were identified from 1000 pregnant Karen women who participated in a placebo randomized controlled trial of chloroquine prophylaxis against P. vivax infection. Cases (n = 136) in the nCC study included all women with Plasmodium infection detected at any time during pregnancy and controls (n = 331) were randomly selected from the 864 women with no detectable parasitemia at any time during pregnancy. Antibodies were measured fortnightly from enrolment to delivery, but only antibody responses at enrolment are included in estimates
mWomen were enrolled up to T3; also measured antibodies at T3 (weeks 30–32), but these estimates are not presented in this review
nPregnant women who were parasite positive (by quantitative PCR) and pregnant women who were parasite negative (quantitative PCR negative) were enrolled during T2 or T3 or at delivery
oAntibody responses were only analysed in women who had at least one detected malarial infection during follow-up
pStudy was conducted using archival samples from pregnant women residing in Yaoundé, Cameroon, including 341 PM+ women and 1036 PM− women
qAnaemia was defined as < 30% packed cell volume
rEstimates included in this review are for IgG3 responses because total IgG was not reported in original paper
sTime points correspond to first- (6–29 weeks) and third- (25–41 weeks) antenatal visits; antibodies were also measured at second visit (16–36 weeks) but data is not included in this review
tWomen selected from a larger cohort of 910 women on the basis of HIV-1 status, gravidity, and placental histology
uOriginal paper grouped women according to placental histology; for this review we combined women who had acute infection with those who had chronic infection, but excluded those with ‘past’ infection
vSevere anaemia defined as Haemoglobin < 70 g/l
wOnly samples from uninfected women were included