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Table 1 Overview of publications by component of maternal, fetal, and newborn outcomes

From: Zika virus infection in pregnancy: a systematic review of disease course and complications

Characteristics

Publications

Study designs

Countries

Reported findings

Other information

Knowledge gaps

Clinical manifestation: maternal, fetal and newborn

McCarthy M., [22]

Ventura C.V., et al., [34]

Ventura C.V., et al., [38]

Villamil-Gómez W.E., et al. [24]

Thomas D.L., et al. [25]

Shuler-Faccini L., et al., [26]

Reyna-Villasmil E., et al. [23]

Oliveira Melo A., el atl., [30]

Mlakar J., et al., [36]

Meaney-Delman D., et al., [37]

Kleber de Oliveira W., et al., [29]

Calvet G., et al. [32]

Brasil Martines R., et al., [27]

Brasil P., et al., [33]

Besnard M, et al., [31]

de Paula Freitas B., et al. [28]

Retrospective cohort

Case series

Case series

Case report

Case report

Retrospective cohort

Case report

Case report

Case report

Case series

Retrospective + Prospect cohort

Case series

Case series

Prospective cohort

Case series

Case series

Brazil

Brazil

Brazil

Colombia

Puerto Rico

Brazil

Venezuela

Brazil

Brazil

USA

Brazil

Brazil

Brazil

Brazil

Brazil

Brazil

Cutaneous rash, maculopapular rash, fever, arthralgia, itch, myalgia, nausea or vomiting, bleeding, respiratory findings, conjunctivitis, malaise, headache, abdominal pain, chills, retroocular pain, edema in lower limbs, hemiparesis, asthenia, jaundice, lumbar pain

Besnard M, et al., reported mild pruritic rash with mild fever (37.5–38 °C) and without fever

- Selection bias based on symptoms suspicious of infection and observed in several studies limits our understanding of ZIKV infection in pregnancy.

- Lack of a detailed history of infection to childbirth or related factors confines our of maternal ZIKV infection.

Clinical manifestations: not reported or vaguely reported

Cauchemez S., et al., [31]

Oliveira Melo A., et al., [30]

Retrospective cohort

Case report

French Polynesia

Brazil

No rash, fever or other infection. Stated as “suffered from symptoms related to Zika virus infection.”

 

- Generalizations or vague reporting limited our understanding of associated ZIKV symptoms

Clinical manifestation: asymptomatic

Sarno M., et al., [35]

Case report

Brazil

No symptoms shown, the first indication of abnormal pregnancy was at ultrasound; intrauterine growth retardation at18 weeks’ gestation

 

The influence of an asymptomatic presentation on management modalities

Trimester infection

Ventura C.V., et al., [34]

Ventura C.V., et al., [38]

Sarno M., et al., [35]

Villamil-Gómez W.E., et al., [24]

Thomas D.L., et al., [25]

Schuler-Faccini L., et al., [26]

Reyna-Villasmil E., et al., [23]

Mlakar J., et al., [36]

Meaney-Delman D., et al., [37]

Calvet G., et al., [32]

Brasil Martines R., et al., [27]

Besnard M., et al., [21]

de Paula Freitas B., et al., [28]

Case series

Case series

Case report

Case report

Case report

Retrospective cohort

Case report

Case report

Case series

Case series

Case series

Case series

Case series

Brazil

Brazil

Brazil

Colombia

Puerto Rico

Brazil

Venezuela

Brazil

USA

Brazil

Brazil

Brazil

Brazil

50 First trimester

22 s trimester

25 Third Trimester

1 Post-partum

Cauchemez S., et al., [30] did not report trimester infection

- Timing of ZIKV infection is critical to maternal and fetal management, however, most studies made only generalised trimester-specific reports

- This restricted our assessment of potential differences in disease susceptibility and progression during pregnancy

Effects on pregnancy complications (maternal)

Reyna-Villasmil E., et al., [23]

Meaney-Delman D., et al., [37]

Brasil Martines R., et al., [27]

Brasil P., et al., [33]

Case report

Case series

Case series

Prospective cohort

Venezuela

USA

Brazil

Brazil

Guillain-Barré Syndrome; decreased muscle movements and difficulty speaking/swallowing, myalgia, fever, rash, and conjunctivitis for 10 days.

Neurological examination showed logical alteration of cranial nerves and speech, decreased muscle strength and respiratory failure.

Four miscarriages (first trimester)

Two stillbirths (fetal deaths after 30 weeks of gestation)

 

- The isolated case of Guillain-Barré Syndrome and other neurological manifestations proposes a need for detailed neurological investigations in the context of ZIKV infection which was lacking

- Proximal causes of stillbirths were not reported

Effects on pregnancy complications (fetus/newborn)

All publications except:

Reyna-Villasmil E., et al., [23]

Thomas D. L. et al., [25]

Case report

Case report

Venezuela

Puerto Rico

Microcephaly, hydraencephaly, macular alterations, optic abnormalities, intra-ocular calcification, cataracts, cerebral (intracranial) calcification, ascites and subcutaneous edema, coarse calcification, cerebellar involvement, severe arthrogryposis, severe central nervous system, affection and gross intrauterine growth retardation, ventriculomegaly

Brasil Martines, R., et al., [26] reported two fetal deaths

Brasil, P., et al., 2016 reported two fetal deaths

All fetal deaths occurred at >30 weeks gestation.

Causes of fetal deaths were unclear

Fetus alterations: frequencies/rates and absolute risk

Kleber de Oliveira W., et al., [29]

Cauchemez S., et al., [31]

Ventura C.V., et al., [34]

Retrospective + Prospective. cohort

Retrospective cohort

Case report

Brazil

French Polynesia

Brazil

Microcephaly had the highest prevalence in the Brazilian states of Pernambuco.

Risk of microcephaly (estimated 1%) 95 cases (34–191) per 1000 women (first trimester) corresponding to a risk ratio of 53.4 (95% CI 6.5–1061–2)

Severe ocular abnormalities when the infection occurs in the first or second trimester of pregnancy

#NR

Lack of clear estimates on the risk of fetal alterations in ZIKV infected pregnant women were observed

Postpartum clinical presentations (maternal)

Besnard M., et al., [21]

Case report

French Polynesia

Post-delivery mild pruritic rash, mild fever (37.5 – 38 °C) and myalgia

#NR

Limited information on maternal progression after childbirth for ZIKV-infected pregnant women

Postpartum clinical presentations (childbirth)

Brasil Martines, R., et al., [27]

Besnard M., et al., [21]

Case report

Case report

Brazil

French Polynesia

Two newborns at 36 and 38 weeks’ gestation with microcephaly who died within 20 h of birth; 1 displayed a maculopapular rash on the 4th day after delivery and thrombocytopenia had severe hypotrophy.

aNR

Limited information on presentations at birth

Other tests

McCarthy M., [21]

Ventura C.V., et al., [22]

Ventura C.V., et al., [38]

Sarno M., et al., [35]

Villamil-Gómez W.E., et al., [24]

Reyna-Villasmil E., et al., [23]

Mlakar J., et al., [36]

Calvet G., et al., [32]

Brasil Martines R., et al., [27]

Brazil P., et al., 2016 [33]

de Paulas Freitas B., et al., 2016 [28]

Retrospective cohort

Case series

Case series

Case report

Case report

Case report

Case report

Case series

Case series

Prospective cohort

Case series

Brazil

Brazil

Brazil

Brazil

Colombia

Venezuela

Brazil

Brazil

Brazil

Brazil

Brazil

Negative serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, or HIV, HTLV, HSV 1 &2, Rheumatoid fever, HBV, VDRL, EBV. Tests for dengue virus, chikungunya virus, toxoplasmosis, rubella virus, cytomegalovirus, Treponema pallidum and parvovirus B19, syphilis.

Ventura, C.V., et al., [33] had positive IgG and negative IgM ELISA results for toxoplasmosis, rubella virus and cytomegalovirus

Villamil-Gómez, W.E., et al., [23] reported one positive (isolating Escherichia coli) trichomonas trophozoites and three positives for Toxoplasma IgG and one for rubella.

Brazil, P., et al., 2016 reported immunity to rubella and cytomegalovirus

Besnard, M., et al., [20] reported dengue negative test results.

- For studies which reported on the presence of coinfections, potential synergy due to the presence of immunity and/or seropositivity to other viruses could not be ascertained

- The effect of coinfections on disease course, consequent maternal, fetal and neonatal outcomes is unknown

  1. ZIKV Zika virus, a NR Not Reported, HTLV Human T-lymphotropic virus, HSV Herpes simplex virus, HBV Hepatitis B virus, VDRL Venereal disease research laboratory test, EBV Epstein-Barr Virus, IgG Immunoglobulin G, IgM Immunoglobulin M, Case report – case description (i.e. symptoms, cause or outcomes, etc.) of an individual patient, Case series – case descriptions (i.e. symptoms, cause or outcomes, etc.) of several patients