Plain english summary
Background
Methods
Search strategy
Selection of studies
Types of studies
Types of participants
Data extraction and synthesis
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 |
Risk of bias assessment
Results
Search results
Characteristics of included studies
Characteristics of maternal ZIKV infection
Symptoms/signs/complications
Characteristics of fetuses/newborns of ZIKV infected pregnant women
Fetuses
Study ID | Sarno M [35] | Villamil Gomez W. E [24] | Thomas D. L [25] | Reyna-Villasmil [23] | Oliveira Melo [30] | Mlakar [36] | Meaney-Delman [37] | Calvet G [32] | Brasil Martines [27] | Besnard M [21] | de Paula Freitas [28] | ||
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1. Was the study question or objective clearly stated? | YES | YES | YES | YES | YES | YES | NO | YES | YES | YES | YES | YES | YES |
2. Was the study population clearly and fully described, including a case definition? | NO | YES | YES | YES | NO | YES | NO | YES | YES | YES | NO | YES | YES |
3. Were the cases consecutive? | YES | YES | NA | YES | NO | NA | YES | NA | YES | YES | YES | YES | YES |
4. Were the subjects comparable? | YES | YES | NA | YES | NO | NA | YES | NA | YES | YES | YES | YES | YES |
5. Was the exposure clearly described? | YES | YES | YES | YES | YES | YES | YES | YES | YES | YES | NO | YES | YES |
6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? | YES | YES | YES | YES | YES | YES | YES | YES | YES | YES | YES | YES | NO |
7. Was the length of follow-up adequate? | NO | YES | YES | YES |
aCD | YES |
aCD | YES |
aCD | YES | NO | NO | NA |
8. Were the statistical methods well-described? | NO | YES | NO | NO | NO | NO |
bNA | NO |
bNA |
bNA |
bNA |
bNA | YES |
9. Were the results well-described? | YES | YES | YES | YES | NO | YES | YES | YES | NO | YES | YES | YES | YES |
Quality Rating (Good, Fair, or Poor) | FAIR | GOOD | GOOD | GOOD Letter to editor | POOR Selective reporting | GOOD Letter to editor | FAIR | GOOD | FAIR | GOOD | FAIR | GOOD | GOOD |
Newborns
Absolute risk of fetal microcephaly (and other birth defects) in women with ZIKV infection
Impact of ZIKV co-infection in pregnancy
Risk of bias assessment
New Castle Ottawa Scale | |||||
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Study ID | McCarthy, M [22] (retrospective cohort study) | Schuler-Faccini [26] (retrospective cohort study) | Kleber de Oliveira [29] (retrospective cohort study) | Cauchemez S [31] (retrospective cohort study) | Brasil Patricia [33] 2016 (prospective cohort study) |
Representativeness of exposed cohort | Not population based (Gotten from a teaching hospital in Salvador, one state) |
a(infants born in eight of Brazil’s states 26 states and reported to the registry) |
a(infants born in three of Brazil’s states 26 states and reported to the registry) |
a(datasets from the French Polynesia Zika virus outbreak) | Not population based (Gotten from centers in Rio de Janeiro, one state) |
Truly representative of the average womana
| |||||
Somewhat representative of the average womana
| |||||
Selected group of users | |||||
No description of the derivation of the cohort | |||||
Selection of non-exposed cohort | No non-exposed cohort | No non-exposed cohort | Only one cohort of exposed individuals | Only one cohort of exposed individuals | Only one cohort of exposed individuals |
Drawn from the same community as the exposed cohorta
| |||||
Drawn from a different source | |||||
No description of the derivation of the non-exposed cohort | |||||
Ascertainment of exposure | No description | No description |
a (Registry) |
a(Serological and surveillance data) |
a(data gotten from clinical and US data) |
Secure records (e.g., surgical records)a
| |||||
Structured interviewa
| |||||
Written self-report | |||||
No description | |||||
Demonstration that outcome of interest not present at study start |
a (Yes, MCP or familial history was excluded) | No | No | No |
a(Yes. No women had had diagnoses of fetal malformations in the current pregnancy before enrollment) |
Yesa
| |||||
No | |||||
Comparability of cohorts on the basis of the design or analysis | Only one cohort of exposed individuals | Only one cohort of exposed individuals | Only one cohort of exposed individuals | Only one cohort of exposed individuals | Only one cohort of exposed individuals |
Study controls for gestational age and/or birth weighta
| |||||
Study controls for any additional factora
| |||||
Assessment of outcome | No description |
a(Record (registry) linkage implied) |
a(Record linkage) |
a(Record linkage from datasets) |
a(Record linkage and self-report as they were followed up weekly by telephone) |
Independent blind assessmenta
| |||||
Record linkagea
Self-report | |||||
No description | |||||
Follow-up long enough for outcomes to occur | No |
a(Yes, for mothers of infants with MCPb born during August to October 2015) |
a(Yes, from January 1, 2015–January 7, 2016) |
a(Yes, over a 23-month study period) |
a(Yes, women were followed up from September 2015 through February 2016) |
Yesa
| |||||
No | |||||
Adequacy of follow-up of cohorts | Not reported |
a(all subjects accounted for) | Not reported |
a(All subjects accounted for) |
a(all subjects accounted for) |
Complete follow-up – all subjects accounted fora
| |||||
Subjects lost to follow-up unlikely to introduce bias or description provided of those losta
| |||||
No statement | |||||
Total number of stars | 1 star | 4 stars | 4 stars | 5 stars | 5 stars |