Table 4. Identified parasitic infection and histopathological changes in preterm birth.

Author, Year	Reported pathogenic microorganism	Diagnostic method	No. of PTB (%)	Infection	Histopathological abnormalities	Triad of histopathology, infection and PTB
Ategeka, 2020 [28]	P. falciparum	Placental blood smear, placental blood for LAMP, placental histopathology	37/637 (5.8%)	51.8% had microscopic parasitemia, and 82.3% had microscopic or submicroscopic parasitemia.	Women randomized to IPTp with SP had a significantly higher prevalence of malaria at delivery compared with women randomized to IPTp with DP: evidence of parasites or malaria pigment by histopathology (61.7% vs 28.2%, P< 0.001).	By binary classification, any malaria parasite or pigment detected by placental histopathology did not increase the risk of preterm birth (aRR 1.09; 95%CI 0.54–2.2, P = 0.82) but was associated with an increased risk for SGA (aRR 2.11; 95%CI 1.25–3.54, P = 0.005). By using the Bulmer classification system, acute-chronic infection (parasite and pigment detected) was not associated with PTB (aRR 1.64; 95%CI 0.47–5.76, P = 0.44), SGA (aRR 0.88; 95%CI 0.21–3.64, P = 0.86) or LBW (aRR 2.01; 95%CI 0.59–6.88, P = 0.27) compared to malaria uninfected samples. However, past-chronic infection (only malaria pigment detected) was associated with increased risk for SGA (aRR 2.14; 95%CI 1.27–3.60, P = 0.004) but not PTB (aRR 1.06; 95%CI 0.51–2.18, P = 0.88).
Kapisi, 2017 [40]	P. falciparum	Microscopy of placental blood smear, LAMP detection of parasite DNA in placental blood, placental histopathology	26/282 (9.2%)	Of 282 women, 52 (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitemia during the pregnancy, 157 (55.7%) had low malaria burden (0–1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+).	Compared to women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups (aRR 3.27; 95%CI 1.32–8.12 and aRR 7.07; 95%CI 2.84–17.6). Detection of placental parasites by any method was significantly associated with PTB (aRR 5.64; 95%CI 1.46–21.8), irrespective of the level of malaria burden during pregnancy.	After adjustment (gravidity, IPTp), PTB was significantly associated with any malaria burden during pregnancy plus placental parasites detected by microscopy of placental blood smear, LAMP detection of dried placental blood spot and placental histopathology (aRR 5.88; 95%CI 1.02–34.0, P = 0.048). Risk of PTB was not significantly associated with any malaria burden during pregnancy when pigment only was detected by placental histopathology (aRR 1.74; 95%CI 0.34–8.96, P = 0.51).
Lufele, 2017 [43]	P. falciparum	Peripheral blood smear (thick and thin films), placental histopathology	81/962a (8.4%)	11.9% (172/1448) experienced symptomatic malaria during their pregnancy.	Of 1451 placentas examined, 18.5% (269/1451) showed evidence of current or past PM. There were 7.5% active infections [3.7% (54/1451) acute, and 3.8% (55/1451) chronic], and 11.0% (160/1451) past infections.	After adjustment for cofounding variables, women with chronic placental malaria infection significantly had an increased risk of PTB compared to malaria uninfected women (OR 3.92; 95%CI 1.64–9.38, P = 0.002). Although acute placental malaria infection was more likely to have PTB, the finding was not significant (OR 2.33; 95%CI 0.86–6.35, P = 0.097).
Saad, 2017 [34]	Toxoplasma Gondii	Anti-toxoplasma gondii IgM and IgG by Indirect haemagglutination assay (sensitivity threshold 8 IU/ml)	37/240 (15.4%)	60 in each group defined as Group A: anti-Toxoplasma IgM and IgG negative; Group B: positive anti-Toxoplasma IgM or IgM seroconversion in mother and neonate; Group C: rising anti-Toxoplasma IgG during pregnancy; Group D: fixed low (non-rising) anti-Toxoplasma IgG during pregnancy.	The common placental histopathological findings in the IgM-positive group (group B) were fibrin deposition, intervillous haemorrhage, villous degeneration and fibrosis, haemorrhage and nearby inflammatory cellular infiltrate and infarction. Group C exhibited higher percentages of inflammatory changes then group D.	The detected abnormal placental findings were calculated and reported as the pathological mean score. This score was significantly higher (P < .001) in IgM-positive cases who ended with miscarriage or PTB (9.28 ± 0.83 and 6.80 ± 0.68, respectively) compared with IgG rising cases with the same pregnancy outcomes (4.88 ± 0.35 and 4.05 ± 0.65, respectively).

Abbreviations: ACA, (acute) chorioamnionitis; aRR, adjusted risk ratio; BMT, basal membrane thickening; CMV, cytomegalovirus; GBS, group B streptococcus; HPV, human papilloma virus, IAI, intra-amniotic inflammation; LAMP, Loop-mediated isothermal amplification; MIAC, microbial invasion of the amniotic cavity; OR, odds ratio; PLMN, polymorphonuclear leuocyte; PPROM, preterm premature rupture of membranes; PRBC, parasitised red blood cell; PTB, preterm birth; SGA, small for gestational age.

^a Total sample size was 1451 participants but only 962 patients had ultrasound scans to determine preterm birth.