Características clínicas, obstétricas y perinatales de embarazadas mexicanas con COVID-19 / Clinical, obstetric and perinatal characteristics of Mexican pregnant women with COVID-19

Introducción: la enfermedad COVID-19 en el embarazo es la primera causa de muerte materna en México, y se ha reportado que favorece las formas graves de la enfermedad. Objetivo: describir las características clínicas, obstétricas y perinatales de pacientes embarazadas con enfermedad COVID-19 atendidas en la UMAE "Luis Castelazo Ayala" del Instituto Mexicano del Seguro Social (IMSS). Material y métodos: estudio observacional, transversal y retrospectivo de pacientes embarazadas con COVID-19 atendidas de marzo a diciembre del 2020. Las características epidemiológicas, complicaciones y resultados perinatales se analizaron con estadística descriptiva e inferencial. Resultados: se incluyeron 133 pacientes: 84.5% presentaron enfermedad leve, 8% moderada y 8.5% severa y crítica. Las comorbilidades preexistentes fueron: obesidad, diabetes e hipotiroidismo. Los principales síntomas: tos, cefalea, fiebre, rinorrea y anosmia. En casos severos y críticos la taquicardia, taquipnea e hipoxemia estuvieron presentes. En las formas severa y crítica se observaron: linfoneutropenia, hiperglucemia y transaminasemia. El fibrinógeno y dímero D sin cambios. El parto pretérmino, el oligohidroamnios, la hipertensión gestacional, la preeclampsia severa y la neumonía fueron las principales complicaciones. El 75% de los recién nacidos no presentaron complicaciones. Conclusiones: el comportamiento clínico de la enfermedad fue, en su mayoría, leve, e incluso en los casos moderados así como en los severos y complicados los resultados del binomio fueron favorables. No hubo muerte materna ni se evidenció transmisión vertical.

Background: COVID-19 disease is the leading cause of maternal death in Mexico. The data published to date indicate that pregnancy favors severe forms of the disease. Objective: To describe the clinical, obstetric and perinatal characteristics of pregnant women with COVID-19 disease treated at the UMAE "Luis Castelazo Ayala" of the Instituto Mexicano del Seguro Social. Material and methods: Observational, cross-sectional and retrospective study of pregnant women with COVID-19 treated from March to December 2020. The epidemiological characteristics, complications and perinatal results were analyzed with descriptive and inferential statistics. Results: 133 patients included: 84.5% with mild disease, 8 % moderate and 8.5% severe and critical. Pre-existing comorbidities: obesity, diabetes and hypothyroidism. Main symptoms: cough, headache, fever, rhinorrhea and anosmia. In severe and critical cases, tachycardia, tachypnea, and hypoxemia were present. Lymphoneutropenia, hyperglycemia, and transaminasemia were seen in severe and critical forms. Fibrinogen and D dimer stayed unchanged. Preterm delivery, oligohydramnios, gestational hypertension, severe preeclampsia, and pneumonia were the main complications. 75% of the newborns without complications. Conclusions: The clinical behavior of the disease was mostly mild and even in moderate cases, and even in moderate as well as severe and complicated cases, the binomial results were favorable. There was no maternal death.

Ligadura de arterias hipogástricas previo al alumbramiento o a la histerectomía obstétrica modificada en inserción anómala de placenta / Ligation of hypogastric arteries prior to delivery or modified obstetric hysterectomy in anomalous insertion of the placenta

Resumen: OBJETIVO: Evaluar las ventajas de practicar o no la ligadura de arterias hipogástricas antes del alumbramiento o previo a la histerectomía modificada en el tratamiento quirúrgico de la inserción anómala de la placenta. MATERIALES Y MÉTODOS: Estudio de serie de casos, retrospectivo, transversal y comparativo efectuado en la Unidad Médica de Alta Especialidad, Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, de 2013 a 2019. Criterios de inclusión: pacientes con inserción anómala de placenta a quienes se practicó o no ligadura de arterias hipogástricas antes del alumbramiento o previo a la histerectomía modificada. Criterios de exclusión: pacientes que no finalizaron el embarazo en el hospital o la información en el expediente estaba incompleta. Parámetros de estudio: sangrado transoperatorio, transfusión sanguínea, morbilidad posoperatoria e ingreso a cuidados intensivos. Los desenlaces se analizaron con estadística descriptiva e inferencial. RESULTADOS: Se evaluaron 285 pacientes; 57% (n = 164) con placenta previa, 27% (n = 78) marginal y 15% (n = 43) normoinserta. El espectro de placenta acreta se encontró en 34% (n = 91) de la muestra. En el grupo de placenta previa la aplicación de la técnica disminuyó el sangrado transoperatorio (p = 0.005) y la transfusión sanguínea (p = 0.05). En pacientes con espectro de placenta acreta hubo una reducción del sangrado transoperatorio (p < 0.01), menores transfusión sanguínea (p = 0.01), ingreso a cuidados intensivos (p < 0.001) y días de estancia en cuidados intensivos (p = 0.0001). CONCLUSIONES: La ligadura de arterias hipogástricas antes del alumbramiento o previo a la histerectomía modificada en el tratamiento quirúrgico de la inserción anómala de la placenta mostró un máximo beneficio en los grupos de placenta previa y espectro de placenta acreta.

Abstract OBJECTIVE: To evaluate the advantages of performing and not performing "Hypogastric artery ligation prior to delivery or modified hysterectomy" in the surgical management of anomalous placental insertion. MATERIALS AND METHODS: A retrospective, cross-sectional, comparative, retrospective case series study conducted at the Unidad Médica de Alta Especialidad, Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, from 2013 to 2019. Inclusion criteria: patients with abnormal placental insertion who underwent hypogastric artery ligation before delivery or before modified obstetric hysterectomy, compared with those who did not have hypogastric artery ligation. Exclusion criteria: patients who did not terminate the pregnancy in the hospital or the information in the file was incomplete. Study parameters: transoperative bleeding, blood transfusion, postoperative morbidity and admission to intensive care. Outcomes were analyzed with descriptive and inferential statistics. RESULTS: 285 patients were evaluated; 57% (n = 164) with placenta previa, 27% (n = 78) marginal and 15% (n = 43) normoinsert. The placenta accreta spectrum was found in 34% (n = 91) of the sample. In the placenta previa group, the application of the technique decreased transoperative bleeding (p = 0.005) and blood transfusion (p = 0.05). In patients with placenta accreta spectrum there was a reduction of transoperative bleeding (p < 0.01), lower blood transfusion (p = 0.01), intensive care admission (p < 0.001) and days of intensive care stay (p = 0.0001). CONCLUSIONS: Hypogastric artery ligation before delivery and before modified hysterectomy in the surgical treatment of anomalous placental insertion showed maximum benefit in the placenta previa and spectrum of placenta accreta groups.

Negative correlation between testosterone and TNF-α in umbilical cord serum favors a weakened immune milieu in the human male fetoplacental unit.

Clinical and epidemiological evidence supports that pregnancies carrying a male fetus are more vulnerable to infections and preterm birth, probably due to testosterone immunosuppressive properties. In human placentas, testosterone lowers the expression of CYP27B1, the vitamin D (VD)-activating enzyme, diminishing cathelicidin synthesis, a potent VD-dependent antimicrobial peptide (AMP). VD also stimulates other AMPs, including defensins. To get insights into the increased male vulnerability mechanisms, we investigated the relationship between fetal sex and the immunoendocrine milieu at the fetoplacental unit. For this, umbilical vein serum and placental samples were collected from healthy newborns. In males' serum, testosterone levels were significantly higher and negatively associated with TNF-α, a cytokine that strengthens the immune response. Males showed lower serum TNF-α and increased levels and gene expression of the immunosuppressive cytokine IL-10. Only in female samples there was a positive association (P < 0.05) between AMPs and both TNF-α and CYP27B1 and between 25-hydroxyvitamin D3 and IL-1ß serum levels. Accordingly, VD-metabolites (25-hydroxyvitamin D3, calcitriol) significantly stimulated IL-1ß gene expression in cultured trophoblasts. Interestingly, IL-1ß mRNA correlated positively with defensins (P < 0.05) in males, but not with cathelicidin expression, which was significantly diminished in comparison to females. Our data suggest that high umbilical serum testosterone and IL-10 in males could explain reduced TNF-α levels and lack of association between VD-dependent innate immunity markers and proinflammatory cytokines expression in the fetoplacental unit. Altogether, our observations imply a restricted basal immune milieu in males compared to females, which may help understand the higher male susceptibility to adverse perinatal outcomes.

Lipopolysaccharide and cAMP modify placental calcitriol biosynthesis reducing antimicrobial peptides gene expression.

PROBLEM: Calcitriol, the hormonal form of vitamin D3 (VD), stimulates placental antimicrobial peptides expression; nonetheless, the regulation of calcitriol biosynthesis in the presence of bacterial products and its consequence on placental innate immunity have scarcely been addressed. METHOD OF STUDY: We investigated how some bacterial products modify placental VD metabolism and its ability to induce antimicrobial peptides gene expression. RESULTS: Cultured human trophoblasts biosynthesized calcitriol only in the presence of its precursor calcidiol, a process that was inhibited by cyclic-AMP but stimulated by lipopolysaccharide (LPS). Intracrine calcitriol upregulated cathelicidin, S100A9, and ß-defensins (HBDs) gene expression, while LPS further stimulated HBD2 and S100A9. Unexpectedly, LPS significantly repressed cathelicidin basal mRNA levels and drastically diminished calcidiol ability to induce it. Meanwhile, cyclic-AMP, which is used by many microbes to avoid host defenses, suppressed calcitriol biosynthesis, resulting in significant inhibition of most VD-dependent microbicidal peptides gene expression. CONCLUSION: While LPS stimulated calcitriol biosynthesis, cyclic-AMP inhibited it. LPS downregulated cathelicidin mRNA expression, whereas cyclic-AMP antagonized VD-dependent-upregulation of most antimicrobial peptides. These findings reveal LPS and cyclic-AMP involvement in dampening placental innate immunity, highlighting the importance of cyclic-AMP in the context of placental infection and suggesting its participation to facilitate bacterial survival.