Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. MATERIALS AND METHODS: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). RESULTS: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). CONCLUSION: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort.

BACKGROUND: In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort. RESULTS: We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism. CONCLUSIONS: Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.

Baby Friendly Hospital Initiative Breastfeeding Outcomes in Mothers with COVID-19 Infection During the First Weeks of the Pandemic in Spain.

BACKGROUND: Adherence to the Ten Steps of the Baby-Friendly Hospital Initiative has been shown to have a protective role for the initiation and maintenance of breastfeeding. RESEARCH AIMS: (1) To determine the breastfeeding rate during the first 6 months of life in children of mothers diagnosed with COVID-19 infection at the time of birth; and (2) to assess the possible influence of being born in a center with Baby-Friendly Hospital Initiative accreditation. METHODS: This was a two-group comparative longitudinal observational study of infants born to mothers with COVID-19 at the time of birth, between March 13-May 31, 2020 (the first wave of the pandemic) in Spain. Fourteen Spanish hospitals participated, five (35.7%) were Baby-Friendly Hospital Initiative accredited. Type of feeding was assessed prospectively at discharge, 1, 3, and 6 months of age. A total of 248 newborns were included in the study. RESULTS: A total of 117 (47.3%) newborns were born in Baby-Friendly Hospital Initiative (BFHI) accredited centers. These centers applied skin-to-skin contact with greater probability (OR = 1.9; 95% CI [1.18, 3.29]) and separated the newborns from their mothers less frequently (OR = 0.46; 95% CI [0.26, 0.81]) than non-accredited centers. No differences were observed in relation to the presence of a companion at the time of birth. At discharge, 49.1% (n = 57) of newborns born in BFHI-accredited centers received exclusive breastfeeding versus 35.3% (n = 46) in non-accredited centers (p = .03). No differences were observed in breastfeeding rates throughout follow-up. CONCLUSIONS: The exclusive breastfeeding rate at discharge in children of mothers with COVID-19 infection at birth was higher in Baby-Friendly Hospital Initiative accredited centers, which most frequently applied skin-to-skin contact at birth as well as rooming-in.

Maternal, Perinatal and Neonatal Outcomes With COVID-19: A Multicenter Study of 242 Pregnancies and Their 248 Infant Newborns During Their First Month of Life.

BACKGROUND: Our aim was to describe the clinical features of mothers with coronavirus disease 2019 (COVID-19) infection during gestation or delivery, and the potential vertical transmission. We also wish to evaluate the possible horizontal transmission after hospital discharge, by means of a follow-up of all the newborns included at 1 month of age. METHODS: This multicenter descriptive study involved 16 Spanish hospitals. We reviewed the medical records of 242 pregnant women diagnosed with COVID-19 from March 13 to May 31, 2020, when they were in their third trimester of pregnancy. They and their 248 newborn infants were monitored until the infant was 1 month old. RESULTS: Caesarean sections (C-sections) were performed on 63 (26%) women. The initial clinical symptoms were coughing (33%) and fever (29.7%). Mothers hospitalized due to COVID-19 pathology had a higher risk of ending their pregnancy via C-section (P = 0.027). Newborns whose mothers had been admitted due to their COVID-19 infection had a higher risk of premature delivery (P = 0.006). We admitted 115 (46.3%) newborn infants to the neonatal unit, of those, 87 (75.6%) were only admitted due to organizational circumstances. No infants died and no vertical or horizontal transmission was detected. Regarding type of feeding, 41.7% of the newborns received exclusive breast-feeding at discharge and 40.4% at 1 month. CONCLUSIONS: We did not detect COVID-19 transmission during delivery or throughout the first month of life in the newborns included in our study. Exclusive breast-feeding rates at discharge and at 1 month of age were lower than expected.

Determinación del sexo fetal en el primer trimestre de la gestación: estudio prospectivo / Fetal gender determination in the first trimester of gestation: a prospective cross-sectional study

Objetivos: Valorar la precisión de la determinación ecográfíca del sexo fetal entre las 11 y las 14 semanas en una cohorte no seleccionada de gestantes. Métodos: Se realizó un estudio prospectivo transversal en una serie consecutiva de 636 gestaciones entre las 11 y 14 semanas, en gestantes que acudieron para el estudio ecográfco rutinario de primer trimestre. Se examinó la región genital del feto en un plano mediosagi-tal, visualizando el signo sagital y la dirección en la que apunta el tubérculo genital (craneal en los varones, caudal en las mujeres) ambos indicadores del sexo fetal. La confrmación clínica del sexo fetal se obtuvo después del parto por confrmación telefónica, o por el cariotipo en casos con amniocentesis por indicaciones convencionales. Resultados: Se consiguió asignar el sexo fetal correctamente en el 86,3 por ciento de los fetos. La precisión de la asignación ecográfca del sexo fetal fue mayor en varones que en mujeres (el 90,6 por ciento de los varones fueron asignados correctamente vs el 83,1 por ciento de las mujeres, p<0,05), y se incrementó con la edad gestacional desde un 72 por ciento entre las 11 y 11+6 semanas, un 92 por ciento entre las 12 y las 12+6 semanas, hasta un 95 por ciento entre las 13 y las 13+6 semanas. Conclusión: La determinación ecográfíca del sexo fetal tiene una elevada tasa de precisión a partir de las 13 semanas, lo que sugiere que las pruebas invasivas para la exclusión de enfermedades ligadas al X podrían obviarse cuando se identifca un feto varón a esta edad gestacional. Sin embargo, en fetos identifcados como mujeres esta decisión deberá posponerse hasta una edad gestacional más avanzada.

Objective: To assess the accuracy of fetal gender determination by ultrasound at 11-14 weeks of gestation in a large cohort of unselected population. Methods: A prospective cross-sectional study was performed in 636 consecutive pregnancies at 11-14 weeks of gestation, attending for frst trimester ultrasound screening. The genital region was examined in the mid-sagittal plane to detect the sagittal sign and the direction in which the genital tubercle pointed (cranial for males, caudal for females) both as markers of fetal gender. The clinical confrmation of fetal gender was obtained from telephonic interviews after delivery or from karyotype in cases scheduled to amniocentesis for conventional indications. Results: Fetal gender was correctly determined by ultrasound in 86.3 percent of the fetuses. The accuracy of sex assignment was higher in male fetuses than in female fetuses (90.6 percent of the males fetuses vs 83.1 percent of the females were correctly assigned, p<0.05) and increased with gestational age from 72 percent at 11-11+6 week's to 92 percent at 12-12+6 week's, and 95 percent at 13-13+6 week's gestation (p<0.01). Conclusion: Prenatal gender assignment by ultrasound has a high accuracy rate at 13 to 13+6 weeks. These results suggest that invasive testing can probably be performed in fetuses identifed as males at this gestational age. However in fetuses identifed as females, the decision regarding invasive testing should be postponed until a higher gestational age is achieved.

[Angiomyolipomas, tuberous sclerosis and pregnancy]. / Angiomiolipomas, esclerosis tuberosa y gestación.

Renal angiomyolipomas are uncommon tumours during pregnancy, but it's important to consider them in the differential diagnosis, for the increased risk of complications such as bleeding, specially during pregnancy. Their characteristics are different depending on if the tumour is associated or not with facomatosis. To show both possibilities, we describe two cases of pregnant women with angiomyolipomas: the first one presented with bleeding of the tumour (Wünderlich's syndrome), but surveillance without treatment was possible until 37th week of gestation, and embolization of the tumour was performed afterwards. The second patient had multiple well known angiomyolipomas, associated to tuberous sclerosis; even though she had required two previous embolizations, she had an uneventful pregnancy, without any episodes of bleeding. Both pregnancies ended successfully by means of a cesarean section. Since there are few papers available in the literature, there is not an agreement about therapeutic management when pregnant women present with bleeding angiomyolipomas (Wünderlich's syndrome). Treatment options include partial or total nephrectomy (with cesarean section simultaneously in patients at 28 weeks of gestation or later), transcateter selective arterial embolization (which can also be preventive), and sometimes, conservative management. If this last option is possible, there's still discussion about the risk of vaginal delivery compared with that of cesarean section, in terms of bleeding of the tumour.

New multiplex PCR for rapid detection of isoniazid-resistant Mycobacterium tuberculosis clinical isolates.

In this study, we describe a multiplex PCR to detect a AGC-->ACC (serine to threonine) mutation in the katG gene and a -15 C-to-T substitution (inhA(C-15T)) at the 5' end of a presumed ribosome binding site in the promoter of the mabA-inhA operon. These mutations have been reported in the majority of previous studies as the most frequent mutations involved in the resistance to isoniazid (INH) of Mycobacterium tuberculosis clinical strains with high levels of resistance. The method was optimized and validated after an analysis of 30 M. tuberculosis clinical isolates with known sequences of the relevant part of the katG gene and the regulatory region of the mabA-inhA operon. We analyzed 297 INH-resistant M. tuberculosis isolates collected in Spain from 1996 to 2003 by PCR-restriction fragment length polymorphism (using the katG gene), DNA sequencing, and the newly developed multiplex PCR. The results were concordant for all 297 isolates tested. The analysis revealed that 204 (68.7%) of the isolates carried one or both of the mutations. This finding suggests that with further development this multiplex PCR will be able to detect the majority of the INH-resistant M. tuberculosis clinical isolates from Spain and other countries where a high frequency of similar mutations occur.