The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Usefulness of lung-to-head ratio and intrapulmonary arterial Doppler in predicting neonatal morbidity in fetuses with congenital diaphragmatic hernia treated with fetoscopic tracheal occlusion.

OBJECTIVE: To explore the potential value of intrapulmonary artery Doppler velocimetry in predicting neonatal morbidity in fetuses with left-sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO). METHODS: Observed/expected lung-to-head ratio (O/E-LHR), and intrapulmonary Doppler pulsatility index and peak early-diastolic reversed flow were evaluated within 24 h before FETO in a consecutive cohort of 51 fetuses with left-sided CDH at between 24 and 33 weeks' gestation. Lung Doppler parameters were converted into Z-scores and defined as abnormal if the pulsatility index had a Z-score of > 1.0 or the peak early-diastolic reversed flow had a Z-score of > 3.5. The association of O/E-LHR and Doppler velocimetry with neonatal outcome was assessed using multiple linear or logistic regression analysis adjusted for gestational age at birth. RESULTS: Among the 26 fetuses that survived, 18 (69.2%) had normal and eight (30.8%) had abnormal Doppler values. O/E-LHR was not associated with neonatal morbidity in surviving fetuses. Compared with the group with normal Doppler parameters, cases with abnormal intrapulmonary Doppler were associated with a significant increase in the duration of mechanical ventilation (average increase of 21.2 (95% CI, 9.99-32.5) days; P < 0.01), conventional ventilation (15.2 (95% CI, 7.43-23.0) days; P < 0.01), high-frequency ventilation (6.34 (95% CI, 0.69-11.99) days; P < 0.05), nitric oxide therapy (5.73 (95% CI, 0.60-10.9) days; P < 0.05), oxygen support (36.5 (95% CI, 16.3-56.7) days; P < 0.01), parenteral nutrition (19.1 (95% CI, 7.53-30.7) days; P < 0.01) and stay in neonatal intensive care unit (42.7 (95% CI, 22.9-62.6) days; P < 0.001), and with significantly higher rates of high-frequency ventilation (87.5 vs. 44.4%;P < 0.05), oxygen requirement at 28 days of age (75.0 vs. 11.1%; P < 0.01), gastroesophageal reflux (62.5 vs. 22.2%; P < 0.05) and tube feeding at discharge (37.5 vs. 5.56%; P < 0.05). CONCLUSION: As previously reported, O/E-LHR did not predict neonatal morbidity. In contrast, intrapulmonary artery Doppler evaluation was predictive of neonatal morbidity in CDH fetuses treated with FETO.

Social and economic factors influencing a fetal surgery program for complicated monochorionic twin pregnancies in a developing country.

OBJECTIVE: To analyze social and economic factors affecting the implementation of a fetal surgery program in a developing country. MATERIALS AND METHODS: During an 18-month period, 30 women with complicated monochorionic diamniotic twin pregnancies were evaluated. 27 women had twin-to-twin transfusion syndrome (TTTS), 2 women had a selective intrauterine growth restriction, and 1 a discordant twin pregnancy with 1 fetus with a severe open neural tube defect. The TTTS cases were treated with fetoscopic laser ablation of the interplacental vascular communications and the remaining 3 cases with bipolar cord occlusion of the affected twin. The patients were evaluated using family income levels (very low, low, median, and high income). Demographic characteristics, gestational age at referral, the prevalence of infections, tocolysis care with hospital readmission, prolonged hospital stay until delivery, and gestational age at delivery were evaluated. RESULTS: The overall survival rate of fetuses treated with laser ablation was 60% (32/54). Survival of at least 1 twin was achieved in 21/27 pregnancies (77%), and survival of both twins in 12/27 pregnancies (44%). The 3 pregnancies treated with cord occlusion had survival of the normal twin. Patients with low and very low family income showed a significantly higher prevalence of vaginal infections, increased periods of tocolysis requiring hospitalization, prolonged hospital stay until the end of pregnancy, and lower gestational age at delivery. CONCLUSION: When a fetal surgery program is implemented in a developing country, social and economic factors will influence the overall healthcare costs and treatment outcomes.

Learning curve for lung area to head circumference ratio measurement in fetuses with congenital diaphragmatic hernia.

OBJECTIVE: To assess the learning curve for the fetal lung area to head circumference ratio (LHR) calculation in fetuses with congenital diaphragmatic hernia (CDH). METHODS: Three trainees with the theoretical knowledge, but without prior experience in the LHR measurement, were selected. Each trainee and one experienced examiner measured the observed to expected (O/E)-LHR in the lung contralateral to the side of the hernia by two methods-manual tracing of lung borders and multiplication of the longest diameters-in a cohort of 95 consecutive CDH fetuses. The average difference between the three trainees and the expert in the O/E-LHR measurement was calculated. A difference below 10% was considered to indicate an accurate measurement. The average learning curve was delineated using cumulative sum analysis (CUSUM). RESULTS: The CUSUM plots demonstrate that the learning curve was achieved by 77 and 72 tests performed for the area obtained by the manual-tracing and multiplication-of-the-longest-diameter methods, respectively. CONCLUSION: The minimum number of scans required for an inexperienced trainee to become competent in examining the LHR is on average 70.

Contribution of intrapulmonary artery Doppler to improve prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion.

OBJECTIVE: To evaluate the contribution of intrapulmonary artery Doppler in predicting the survival of fetuses with congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO). METHODS: A cohort of 41 fetuses (between 24 and 28 weeks of gestation) with CDH was treated with FETO. The observed/expected lung-to-head ratio (O/E-LHR), pulmonary artery pulsatility index (PI), peak early diastolic reversed flow (PEDRF) and peak systolic velocity (PSV) were evaluated before FETO, and their isolated and combined value to predict survival using multiple logistic regression and decision-tree analysis was assessed. RESULTS: O/E-LHR and intrapulmonary artery PI and PEDRF were significantly associated with the probability of survival (O/E-LHR > or = 26%, OR 14.2; PI < 1 Z-score, OR 8.4; and PEDRF < 3.5 Z-scores, OR 5.7). Decision-tree analysis showed that O/E-LHR was the best initial predictor of prognosis (O/E-LHR > or = 26%, 90% survival; O/E-LHR < 26%, 45% survival). For fetuses with an O/E-LHR of < 26%, Doppler parameters allowed discrimination of cases with moderate (66-71% survival) and very poor (0% survival) prognosis. CONCLUSION: Intrapulmonary artery Doppler evaluation helps to refine the prediction of survival after FETO in fetuses with severe CDH.

Lung tissue perfusion in congenital diaphragmatic hernia and association with the lung-to-head ratio and intrapulmonary artery pulsed Doppler.

OBJECTIVE: To evaluate lung tissue perfusion in fetuses with congenital diaphragmatic hernia (CDH) and to explore the association of lung tissue perfusion with the lung area to head circumference ratio (LHR) and intrapulmonary artery pulsed Doppler. METHODS: Fetuses with isolated left CDH were evaluated and compared with a group of fetuses without CDH, which were sampled from our general population and matched by gestational age at inclusion. Lung tissue perfusion measured using fractional moving blood volume (FMBV), the observed to expected (O/E) LHR and pulsed Doppler of the proximal intrapulmonary artery were evaluated in the lung contralateral to the side of the hernia. Doppler waveform analysis included the pulsatility index (PI), the peak early diastolic reversed flow (PEDRF) and the peak systolic velocity (PSV). All Doppler parameters were converted into Z-scores for gestational age. The associations between FMBV and O/E-LHR and between FMBV and intrapulmonary arterial Doppler parameters were analyzed using multiple linear regression, adjusted by gestational age. RESULTS: A total of 190 fetuses (95 with CDH and 95 controls) were evaluated. Fetuses with CDH showed significantly lower lung FMBV (26.8 (SD 8.4) vs. 37.9 (SD 8.1)%; P < 0.001) than controls. Lung tissue perfusion correlated positively with O/E-LHR (r = 0.37; P < 0.001) and negatively with intrapulmonary artery PI (r = - 0.31; P < 0.001), PEDRF (r = - 0.43; P < 0.001) and PSV (r = - 0.18; P = 0.03). CONCLUSIONS: Fetuses with CDH have decreased lung tissue perfusion, which is associated with decreased lung growth and increased intrapulmonary artery impedance.

Association between intrapulmonary arterial Doppler parameters and degree of lung growth as measured by lung-to-head ratio in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: To describe the association between the intrapulmonary circulation and the degree of lung growth in fetuses with congenital diaphragmatic hernia (CDH). METHODS: Thirty-six fetuses with isolated left CDH at 22-29 weeks of gestation were studied. Four groups were defined according to lung-to-head ratio (LHR), expressed as the ratio of observed to expected LHR for gestational age (O/E LHR). Pulsatility index (PI), peak systolic velocity (PSV), peak early-diastolic reversed flow (PEDRF), end-diastolic velocity (EDV), acceleration time (AT), time averaged velocity (TAV) and the ratio AT to ejection time (AT/ET) were measured in all fetuses in the proximal arterial branch of both lungs. For analysis, Doppler values were converted to Z-scores. RESULTS: It was possible to record all Doppler parameters from the contralateral lung of all CDH fetuses, and from the ipsilateral lung in 28 (77.7%). PEDRF significantly increased in relation to the decrease in O/E LHR in both lungs (contralateral: r = - 0.65, P = 0.01; ipsilateral: r = - 0.43, P = 0.02). PI increased significantly with the reduction in O/E LHR but only on the side contralateral to the hernia (r = - 0.55, P = 0.02). In the ipsilateral pulmonary artery, PI values showed a significant overall increase but no differences were observed among the O/E LHR groups. PSV, EDV and TAV were reduced in both lungs with respect to normal values, but no association was found with the O/E LHR. No changes in AT or AT/ET were observed in either lung. CONCLUSIONS: PEDRF is quick and easy to calculate, and showed the strongest and most consistent correlation with O/E LHR. The association between PEDRF and LHR might be an additional parameter that could help to establish prognosis in fetuses with CDH.