However, detrimental actions of interleukin-1 and other pro-inflammatory cytokines in infected placentas are involved in adverse neonatal outcomes, suggesting that tightly regulated immune responses are crucial to sustain placenta homeostasis.208 Besides, human trophoblasts-associated antiviral microRNAs, such as chromosome 19 miRNA cluster that are packaged into placental exosomes, were also systemically isolated from CENPA pregnant women, which operate in a paracrine or autocrine manner to resist infection.209,210 Mechanistically, primary human trophoblast-derived chromosome 19 miRNA cluster family members drastically 5(6)-Carboxyfluorescein limited both RNA and DNA viral infections in non-placental cells by inducing autophagy, demonstrating a unique placenta-secreted effector for shielding virus-sensitive cells in placenta from infections.198,211 The neonatal fragment crystallizable receptor (FcRn) mediated antibodies transplacental transfer Transplacental passage of IgG begins in the first trimester of pregnancy and lasts until labor, which sets up another layer of fetal protection from viral infections.212 Generally, endocytosis of IgG from maternal blood was initiated by binding to a canonical IgG shuttle receptor, FcRn, around the apical side of STBs. fight the next emerging and re-emerging infectious disease in the pregnancy populace. family, is the most common blood-borne pathogen globally, which could lead to acute and chronic 5(6)-Carboxyfluorescein hepatitis in humans. The transmission routes of HBV are predominantly through blood and bodily fluids, vertical transmission, as well as sexual and parenteral contacts.9 Perinatal transmission from the mother to fetus or newborns is still responsible for the most chronic HBV infections in adults who are more prone to severe liver diseases and poor responses to antiviral therapies.10,11 The risk of perinatal transmission in case of mothers with positive HBV e antigen or high viral loads has been estimated to be as high as 90% if the newborns accept no immunoprophylaxis treatment (includes HBV vaccine and immune globulin).12 Therefore, to prevent the vertical transmission of HBV in advance, universal maternal screenings for the HBV surface antigen, HBV e antigen, viral load, and alanine aminotransferase level during pregnancy are priorities to be adopted.12 Although immunoprophylaxis at birth together with antiviral treatments for mothers in endemic areas currently are the common and effective strategies for global elimination and preventive interventions of HBV, vertical transmission of HBV occurs with high prevalence and should be taken seriously due to uneven coverage of vaccine globally and/or prophylaxis failure.13C15 Although pregnancy complications related to HBV infection if any are minimal, clinical evidence has indicated that chronic HBV infection may be vaguely associated with gestational diabetes, preterm labor, antepartum hemorrhage, and preeclampsia.16C18 For preterm birth, several meta-analyses have confirmed that seropositivity for HBV surface antigen in pregnant women could increase the risk of preterm labor, while another study involving 6781 prematurity cases inconsistently revealed no association with HBV contamination in the preterm birth group.17,19C22 Worthy of note, in the above-mentioned studies, half of the enrolled pregnant women exhibited abnormal liver functions such as nonalcoholic fatty liver disease, which may be an independent risk factor for preterm labor rather than the computer virus per se. Interestingly, women with HBV contamination were observed to develop 2.18-fold higher antepartum hemorrhage, probably due to placenta previa and placental abruption, which is attributed to coinfection of HBV with other viruses.21 Unexpectedly, a negative association or protective effect of HBV contamination on preeclampsia was demonstrated in a meta-analysis involving 11,566 cases.23 Nonetheless, the explicit causes underlying the above adverse pregnancy outcomes have not been extensively evaluated until now, placental inflammation, insulin resistance, increased 5(6)-Carboxyfluorescein immunotolerance, or impaired immune response upon HBV infection were proposed as suspected mechanisms.18,24 Furthermore, the hint of fetal and neonatal anomalies was also observed in pregnant women with chronic infection. It was noticed that 60% increased non-reassuring fetal heart rate patterns and 80% increase in asphyxia referring to 7600 pregnant HBV carriers from 18 studies by meta-analysis suggested fetal distress conditions related to HBV contamination.25,26 Additionally, 25.8% increased low birth weight and small infants were reported to be associated with HBV infection, while abnormally enhanced fetal growth and macrosomia were also found in a series of researches.26C28 Viral genotypes, co-existing hepatic disorders, coinfections with other pathogenic organisms, synergism with pregnancy complications, and the phase of chronic HBV infection probably led to contradictory phenotypes of fetal growth.29,30 The path of HBV vertical transmission includes intrauterine transmission, labor, and delivery, as well as breastfeeding. The primary risk period for infant HBV contamination is the peripartum period. Most cases of contamination occur during delivery when the mucosa of newborns is usually easily contaminated by maternal blood and secretions that contain.