Emerging and re-emerging infectious diseases in pregnant women in an amazonian region: a large retrospective study from French Guiana.

PURPOSE: Over the past decade, the Amazon basin has faced numerous infectious epidemics. Our comprehension of the actual extent of these infections during pregnancy remains limited. This study aimed to clarify the clinical and epidemiological features of emerging and re-emerging infectious diseases during pregnancy in western French Guiana and along the Maroni River over the previous nine years. METHODS: This retrospective cohort study enrolled pregnant women living in west French Guiana territory and giving birth in the only local referral center after 22 weeks of gestation between 2013 and 2021. Data on symptomatic or asymptomatic biologically confirmed emerging or re-emerging diseases during pregnancy was collected. RESULTS: Six epidemic waves were experienced during the study period, including 498 confirmed Zika virus infections (2016), 363 SARS-CoV-2 infections (2020-2021), 87 chikungunya virus infections (2014), 76 syphilis infections (2013-2021), and 60 dengue virus infections (2013-2021) at different gestational ages. Furthermore, 1.1% (n = 287) and 1.4% (n = 350) of pregnant women in west French Guiana were living with HIV and HTLV, respectively. During the study period, at least 5.5% (n = 1,371) faced an emerging or re-emerging infection during pregnancy. CONCLUSION: These results highlight the diversity, abundance, and dynamism of emerging and re-emerging infectious agents faced by pregnant women in the Amazon basin. Considering the maternal and neonatal adverse outcomes associated with these infections, increased efforts are required to enhance diagnosis, reporting, and treatment of these conditions.

Causes and consequences of fever in Amazonian pregnant women: A large retrospective study from French Guiana.

OBJECTIVE: The aim of this study was to describe different causes and consequences of fever during pregnancy in Western French Guiana and along the Maroni River. STUDY DESIGN: A retrospective single-center study including all patients with a history of documented fever ≥ 38°C during pregnancy at the West French Guiana Hospital for 9 years. Postpartum fever and nosocomial infections were excluded. We focused on medical history and on clinical and biological findings. Causes were characterized as confirmed or uncertain and then classified as preventable or non-preventable. RESULTS: A total of 940 pregnant women who experienced at least one episode of fever were included and compared to 23,811 deliveries who occurred during the same period without documented fever. Among them, 43.7% (411/940) were in labor. About 3.7% (35/940) of febrile pregnant women had at least two episodes of fever, while 0.3% (3/940) had a coinfection at the time of diagnosis, resulting in a total of 978 febrile episodes. Among them, causes remained unknown or uncertain in 7.6% (75/978) and 0.9% (9/978) of cases, respectively. Among confirmed causes of fever throughout pregnancy (n = 483), the most common known cause was arbovirus infection (146/483, 30.2%), followed by urinary tract infection (134/483, 27.7%), chickenpox (27/483, 5.6%), and gastrointestinal (14/483, 2.9%) and pulmonary infections (10/483, 2%). Mothers with fever had a higher risk of cesarean section (19.8% vs 15.5%, aOR 1.3 [95% CI 1.14-1.6], stillbirth (5.5% versus 1.9%, aOR 2.7 [95% CI 2-3.7]), and preterm delivery < 34 weeks of gestation (7.2% vs 4.7%, aOR 1.5 [95% CI 1.2-2]. CONCLUSIONS: In the Amazon region, causes of fever are diverse and often associated with epidemic waves, notably arboviruses. This must be considered when exploring possible causes of fever during pregnancy in these localities, including fetal anomalies and/or fetal loss. Physicians should consider the epidemiological context and avoid generalizations. Given the impact of emergent agents such as arboviruses on pregnancy, particular attention must be paid to the epidemiological context. This study can also help clinicians when managing fever in pregnant travelers or in their partner after having visited exposed areas. In this context, fetal abnormalities and adverse obstetric outcomes should be explored accordingly.

Tonate Virus and Fetal Abnormalities, French Guiana, 2019.

We report a case of vertical transmission of Tonate virus in a pregnant woman from French Guiana. The fetus showed severe necrotic and hemorrhagic lesions of the brain and spinal cord. Clinicians should be made aware of possible adverse fetal outcomes in pregnant women infected with Tonate virus.

Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life.

Little is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5-29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2-20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9-10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

Maternal Infection and Adverse Pregnancy Outcomes among Pregnant Travellers: Results of the International Zika Virus in Pregnancy Registry.

In this multicentre cohort study, we evaluated the risks of maternal ZIKV infections and adverse pregnancy outcomes among exposed travellers compared to women living in areas with ZIKV circulation (residents). The risk of maternal infection was lower among travellers compared to residents: 25.0% (n = 36/144) versus 42.9% (n = 309/721); aRR 0.6; 95% CI 0.5-0.8. Risk factors associated with maternal infection among travellers were travelling during the epidemic period (i.e., June 2015 to December 2016) (aOR 29.4; 95% CI 3.7-228.1), travelling to the Caribbean Islands (aOR 3.2; 95% CI 1.2-8.7) and stay duration >2 weeks (aOR 8.7; 95% CI 1.1-71.5). Adverse pregnancy outcomes were observed in 8.3% (n = 3/36) of infected travellers and 12.7% (n = 39/309) of infected residents. Overall, the risk of maternal infections is lower among travellers compared to residents and related to the presence of ongoing outbreaks and stay duration, with stays <2 weeks associated with minimal risk in the absence of ongoing outbreaks.

Prolonged Maternal Zika Viremia as a Marker of Adverse Perinatal Outcomes.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal-fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus-infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January-July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9-57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0-15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9-5.5]).

Maternal, fetal and neonatal outcomes of large series of SARS-CoV-2 positive pregnancies in peripartum period: A single-center prospective comparative study.

OBJECTIVE: To describe the proportions of asymptomatic, mild and severe diseases in infected pregnant women admitted for delivery. To compare maternal, fetal and neonatal outcomes of SARS-CoV-2 infected pregnant women with those of non-infected patients. STUDY DESIGN: Through an universal PCR testing for SARS-COV-2 at admission (not symptoms-based), this prospective cohort study enrolled all pregnant women admitted for delivery between 16th of June and the 16th of August 2020 in the West French Guiana Hospital Center. RESULTS: 507 pregnant women were included during the study period, of which 137 (27 %) were infected with SARS-COV-2. On admission, only 34/137 (24.8 %) of these patients presented with clinical symptoms. Among asymptomatic women, 16 /103 (15 %) became symptomatic after diagnosis. Throughout the delivery hospitalization and follow-up, 87/137 (63.5 %) remained always asymptomatic, 45/137 (32.8 %) developed a mild COVID-19 and 5/137 (3.6 %) developed a severe infection. SARS-CoV-2 infected patients were more likely to have post-partum hemorrhage >500 mL (14.2 % vs 7.2 %, RR 2.0 [95 %CI 1.1-3.4]), to be transfused (5.5 % vs 1.1 %, RR 4.9 [1.5-16.6]), and to be hospitalized in ICU (3.6 % vs 0.8 %, RR 4.5 [95 %CI 1.1-18.6] than uninfected ones. Intra-uterine fetal demises were more common in infected mothers compared to controls (5.1 % vs 1.1 %, RR 4.7 [95 % CI 1.4-45.9). Among 108 neonates from infected mothers tested at birth, none tested positive (0/108). When tested between 25 and 42 h after delivery, 4/29 (13.7 %) were positive for SARS-CoV-2 RT-PCR on nasopharyngeal swabs and remained asymptomatic. CONCLUSION: Pregnant women admitted for delivery and diagnosed with a SARS-COV-2 infection through an universal screening were symptomatic in only a quarter of cases. Their risks of post-partum hemorrhage, transfusion and admission to ICU were higher than those of uninfected patients. They also presented a higher risk of intra-uterine fetal demise. There were no other differences in maternal, obstetrical or neonatal outcomes.

Another piece of the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

BACKGROUND: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. RESULTS: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. CONCLUSION: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.

Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana.

OBJECTIVES: To estimate the rates of maternal-fetal transmission of Zika virus, adverse fetal/neonatal outcomes, and subsequent rates of asymptomatic/symptomatic congenital Zika virus infections up to the first week of life. DESIGN: Cohort study with prospective data collection and subsequent review of fetal/neonatal outcomes. SETTINGS: Referral centre for prenatal diagnosis of the French Guiana Western Hospital. PARTICIPANTS: Pregnant women at any stage of pregnancy with a laboratory confirmed symptomatic or asymptomatic Zika virus infection during the epidemic period in western French Guiana. The cohort enrolled 300 participants and prospectively followed their 305 fetuses/newborns. MAIN OUTCOME MEASURES: Rate of maternal-fetal transmission of Zika virus (amniotic fluid, fetal and neonatal blood, urine, cerebrospinal fluid, and placentas); clinical, biological, and radiological outcomes (blindly reviewed); and adverse outcomes defined as moderate signs potentially related to congenital Zika syndrome (CZS), severe complications compatible with CZS, or fetal loss. Associations between a laboratory confirmed congenital Zika virus infection and adverse fetal/neonatal outcomes were evaluated. RESULTS: Maternal-fetal transmission was documented in 26% (76/291) of fetuses/newborns with complete data. Among the Zika virus positive fetuses/newborns, 45% (34/76) presented with no signs/complications at birth, 20% (15/76) with moderate signs potentially related to CZS, 21% (16/76) with severe complications compatible with CZS, and 14% (11/76) with fetal loss. Compared with the Zika virus positive fetuses/neonates, those that were identified as negative for Zika virus (215/291) were less likely to present with severe complications (5%; 10/215) or fetal loss (0.5%; 1/215; relative risk 6.9, 95% confidence interval 3.6 to 13.3). Association between a positive Zika virus test and any adverse fetal/neonatal outcome was also significant (relative risk 4.4, 2.9 to 6.6). The population attributable fraction estimates that a confirmed congenital Zika virus infection contributes to 47% of adverse outcomes and 61% of severe adverse outcomes observed. CONCLUSION: In cases of a known maternal Zika virus infection, approximately a quarter of fetuses will become congenitally infected, of which a third will have severe complications at birth or fetal loss. The burden of CZS might be lower than initially described in South America and may not differ from other congenital infections.