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      Infections at the maternal–fetal interface: an overview of pathogenesis and defence

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          Abstract

          Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym ‘TORCH’ ( Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

          Abstract

          Infections during pregnancy can be associated with devastating outcomes for the pregnant mother and developing fetus. In this Review, Megli and Coyne discuss placental defences and provide an overview of how various viral, bacterial and parasitic pathogens traverse the maternal–fetal interface and cause disease.

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          Most cited references227

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          Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

          Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.
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            Single-cell reconstruction of the early maternal–fetal interface in humans

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              Stillbirths: rates, risk factors, and acceleration towards 2030

              An estimated 2.6 million third trimester stillbirths occurred in 2015 (uncertainty range 2.4-3.0 million). The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030. 94 mainly high-income countries and upper middle-income countries have already met this target, although with noticeable disparities. At least 56 countries, particularly in Africa and in areas affected by conflict, will have to more than double present progress to reach this target. Most (98%) stillbirths are in low-income and middle-income countries. Improved care at birth is essential to prevent 1.3 million (uncertainty range 1.2-1.6 million) intrapartum stillbirths, end preventable maternal and neonatal deaths, and improve child development. Estimates for stillbirth causation are impeded by various classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7.4% of stillbirths. Many disorders associated with stillbirths are potentially modifiable and often coexist, such as maternal infections (population attributable fraction: malaria 8.0% and syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors (each about 10%), and maternal age older than 35 years (6.7%). Prolonged pregnancies contribute to 14.0% of stillbirths. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour, or both. Two-thirds of newborns have their births registered. However, less than 5% of neonatal deaths and even fewer stillbirths have death registration. Records and registrations of all births, stillbirths, neonatal, and maternal deaths in a health facility would substantially increase data availability. Improved data alone will not save lives but provide a way to target interventions to reach more than 7000 women every day worldwide who experience the reality of stillbirth.
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                Author and article information

                Contributors
                cjm232@pitt.edu
                carolyn.coyne@duke.edu
                Journal
                Nat Rev Microbiol
                Nat Rev Microbiol
                Nature Reviews. Microbiology
                Nature Publishing Group UK (London )
                1740-1526
                1740-1534
                25 August 2021
                : 1-16
                Affiliations
                [1 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Division of Maternal–Fetal Medicine, Division of Reproductive Infectious Disease, Department of Obstetrics, Gynecology and Reproductive Sciences, , University of Pittsburgh School of Medicine and the Magee Womens Research Institute, ; Pittsburgh, PA USA
                [2 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Department of Molecular Genetics and Microbiology and the Duke Human Vaccine Institute, , Duke University School of Medicine, ; Durham, NC USA
                Author information
                http://orcid.org/0000-0002-6579-3908
                http://orcid.org/0000-0002-1884-6309
                Article
                610
                10.1038/s41579-021-00610-y
                8386341
                34433930
                c9ce033f-2520-4d52-8481-413aa62093a9
                © Springer Nature Limited 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 15 July 2021
                Categories
                Review Article

                bacteria,virology,parasitology,antimicrobial responses,infectious diseases

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