Congenital diaphragmatic hernia treated via fetal endoscopic tracheal occlusion improves outcome in a middle-income country.

OBJECTIVES: A recent European randomized trial - Tracheal Occlusion To Accelerate Lung Growth - demonstrated that fetoscopic endoluminal tracheal occlusion (FETO) is associated with increased postnatal survival among infants with severe congenital diaphragmatic hernia (CDH). However, this differs in middle-income countries such as Brazil, where abortion is illegal and neonatal intensive care is inadequate. This study evaluated the effects of FETO on improving the survival of infants with moderate-to-severe CDH in isolated and non-isolated cases. METHODS: This retrospective cohort study selected 49 fetuses with CDH, a normal karyotype, and a lung-to-head ratio (LHR) of <1 from a single national referral center for fetal surgery in São Paulo, Brazil, between January 2016 and November 2019. FETO was performed between 26 and 29 weeks of gestation. The primary outcomes were infant survival until discharge from the neonatal intensive care unit and survival until six months of age. RESULTS: Forty-six women with singleton fetuses having severe CDH underwent prenatal intervention with FETO. Infant survival rates until discharge and at six months of age were both 38 %. The observed-to-expected LHR increased by 25 % after FETO in neonates who survived until discharge. Spontaneous intrauterine death occurred in four growth-restricted fetuses after FETO. Preterm birth in <37 weeks and preterm rupture of membranes in <34 weeks occurred in 56.5 % (26) and 26 % (12) cases, respectively. CONCLUSIONS: FETO may increase neonatal survival in fetuses with severe CDH, particularly in countries with limited neonatal intensive care.

Predicting insulin use among women with gestational diabetes diagnosed in oral glucose tolerance test.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications affecting pregnant women. While most women will achieve adequate glycemic levels with diet and exercise, some will require pharmacological treatment to reach and maintain glucose levels between the desired thresholds. Identifying these patients early in pregnancy could help direct resources and interventions. METHODS: This retrospective cohort of women with GDM diagnosed with an abnormal 75g-OGTT presents data from 869 patients (724 in the diet group and 145 in the insulin group). Univariate logistic regression was used to compare the groups, and multivariable logistic regression was used to identify independent factors associated with the need for insulin. A log-linear function was used to estimate the probability of requiring pharmacological treatment. RESULTS: Women in the insulin group had higher pre-pregnancy BMI index (29.8 vs 27.8 kg/m2, odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09), more frequent history of previous GDM (19.4% vs. 7.8%, OR 2.84, 95% CI 1.59-5.05), were more likely to have chronic hypertension (31.7% vs. 23.2%, OR 1.54, 95% CI 1.04-2.27), and had higher glucose levels at all three OGTT points. Multivariable logistic regression final model included age, BMI, previous GDM status, and the three OGTT values as predictors of insulin requirement. CONCLUSIONS: We can use regularly collected data from patients (age, BMI, previous GDM status, and the three OGTT values) to calculate the risk of a woman with GDM diagnosed in OGTT needing insulin. Identifying patients with a greater risk of requiring pharmacological treatment could help healthcare services to better allocate resources and offer closer follow-up to high-risk patients.

Bacterial profile and prevalence of urinary tract infections in pregnant women in Latin America: a systematic review and meta-analysis.

BACKGROUND: Given the physiological changes during pregnancy, pregnant women are likely to develop recurrent urinary tract infections (UTIs) and pyelonephritis, which may result in adverse obstetric outcomes, including prematurity and low birth weight preeclampsia. However, data on UTI prevalence and bacterial profile in Latin American pregnant women remain scarce, necessitating the present systematic review to address this issue. METHODS: To identify eligible observational studies published up to September 2022, keywords were systematically searched in Medline/PubMed, Cochrane Library, Embase, Web of Science, and Bireme/Lilacs electronic databases and Google Scholar. The systematic review with meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the quality of studies was classified according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The meta-analysis employed a random-effects method with double-arcsine transformation in the R software. RESULTS: Database and manual searches identified 253,550 citations published until September 2022. Among the identified citations, 67 met the inclusion criteria and were included in the systematic review, corresponding to a sample of 111,249 pregnant women from nine Latin American countries. Among Latin American pregnant women, the prevalence rates of asymptomatic bacteriuria, lower UTI, and pyelonephritis were estimated at 18.45% (95% confidence interval [CI]: 15.45-21.53), 7.54% (95% CI: 4.76-10.87), and 2.34% (95% CI: 0.68-4.85), respectively. Some regional differences were also detected. Among the included studies, Escherichia coli (70%) was identified as the most frequently isolated bacterial species, followed by Klebsiella sp. (6.8%). CONCLUSION: Pregnant women in Latin America exhibit a higher prevalence of bacteriuria, UTI, and pyelonephritis than pregnant women globally. This scenario reinforces the importance of universal screening with urine culture during early prenatal care to ensure improved outcomes. Future investigations should assess the microbial susceptibility profiles of uropathogens isolated from pregnant women in Latin America. TRIAL REGISTRATION: This research was registered at PROSPERO (No. CRD42020212601).

Risk factors for shunting at 12 months following open fetal repair of spina bifida by mini-hysterotomy.

OBJECTIVES: Open spina bifida (OSB) is the most common neural tube defect. Prenatal repair reduces the need for ventriculoperitoneal shunting (VPS) due to hydrocephalus from 80-90% to 40-50%. We aimed to determine which variables work as risk factors for VPS at 12 months of age in our population. METHODS: Thirty-nine patients underwent prenatal repair of OSB by mini-hysterotomy. The main outcome was occurrence of VPS in the first 12 months of life. Logistic regression was used to estimate the odds ratios (OR) between prenatal variables and the need for shunting. RESULTS: VPS at 12 months occurred in 34.2% of the children. Larger ventricle size before surgery (62.5% ≥15 mm; 46.2% between 12 and 15 mm; 11.8% <12 mm; p=0.008), higher lesion level (80% >L2, vs. 17.9% ≤L3; p=0.002; OR, 18.4 [2.96-114.30]), and later gestational age at surgery (25.25 ± 1.18 vs. 24.37 ± 1.06 weeks; p=0.036; OR, 2.23 [1.05-4.74]) were related to increased need for shunting. In the multivariate analysis, larger ventricle size before surgery (≥15 mm vs. <12 mm; p=0.046; OR, 1.35 [1.01-1.82]) and higher lesion level (>L2 vs. ≤L3; p=0.004; OR, 39.52 [3.25-480.69]) were risk factors for shunting. CONCLUSIONS: Larger ventricle size before surgery (≥15 mm) and higher lesion level (>L2) are independent risk factors for VPS at 12 months of age in fetuses undergoing prenatal repair of OSB by mini-hysterotomy in the studied population.

Three-Dimensional Ultrasound Evaluation of Lung Volume in Fetuses with Abdominal Wall Defect.

INTRODUCTION: Abdominal wall defects (AWDs) interfere with postnatal respiratory parameters. We aimed to evaluate lung volume (LV) in fetuses with AWD using three-dimensional (3D) ultrasound (US) and to correlate AWD with the type (omphalocele and gastroschisis) and size of the defect and neonatal morbidity and mortality. METHODS: This prospective observational study included 72 pregnant women with fetuses with AWD and a gestational age <25 weeks. The data on abdominal volume, 3D US LV, and herniated volume were acquired every 4 weeks up to 33 weeks. LV was compared with normal reference curves and correlated with abdominal and herniated volumes. RESULTS: Omphalocele (p < 0.001) and gastroschisis (p < 0.001) fetuses had smaller LV than normal fetuses. LV was positively correlated with abdominal volume (omphalocele, r = 0.86; gastroschisis, r = 0.88), whereas LV was negatively correlated with omphalocele-herniated volume/abdominal volume (p < 0.001, r = -0.51). LV was smaller in omphalocele fetuses that died (p = 0.002), were intubated (p = 0.02), or had secondary closure (p < 0.001). In gastroschisis, a smaller LV was observed in fetuses discharged using oxygen (p = 0.002). CONCLUSION: Fetuses with AWD had smaller 3D LV than normal fetuses. Fetal abdominal volume was inversely correlated with LV. In omphalocele fetuses, a smaller LV was associated with neonatal mortality and morbidity.

Lung ultrasound versus chest computed tomography for pregnant inpatients with COVID-19.

PURPOSE: To compare lung ultrasound (US) and computed tomography (CT) in the assessment of pregnant women with COVID-19. METHODS: Prospective study comprising 39 pregnant inpatients with COVID-19 who underwent pulmonary assessment with CT and US with a maximum span of 48 h between the exams. The thorax was divided into 12 regions and assessed in terms of the following: the presence of B-lines (>2), coalescent B-lines, consolidation on US; presence of interlobular thickening, ground glass, consolidation on CT. The two methods were scored by adding up the scores from each thoracic region. RESULTS: A significant correlation was found between the scores obtained by the two methods (rICC = 0.946; p < 0.001). They were moderately in agreement concerning the frequency of altered pulmonary regions (weighted kappa = 0.551). In US, a score over 15, coalescent B-lines, and consolidation were predictors of the need for oxygen, whereas the predictors in CT were a lung score over 16 and consolidation. The two methods, US (p < 0.001; AUC = 0.915) and CT (p < 0.001; AUC = 0.938), were fairly accurate in predicting the need for oxygen. CONCLUSION: In pregnant women, lung US and chest CT are of similar accuracy in assessing lungs affected by COVID-19 and can predict the need for oxygen.

Sonographic evaluation of umbilical cord thickness in monochorionic diamniotic twin pregnancies.

OBJECTIVE: To develop a nomogram of the thickness of the umbilical cord (UC) and its components in monochorionic diamniotic (MCDA) twin pregnancies. METHODS: This prospective longitudinal study involved 47 MCDA twin pregnancies (94 fetuses) between 18 and 33 weeks of gestation. Ultrasound assessments of UC cross-sections and measurements of the umbilical cord area (UCA), the umbilical vein area (UVA), the umbilical artery area (UAA), and the Wharton jelly area (WJA) were made. The UC measurements were correlated with gestational ages. Reference values for the gestational ages of MCDA pregnancies were determined and compared with those of dichorionic twins and singletons. The cases which developed selective intrauterine growth restriction were contrasted with normal cases. RESULTS: A positive correlation was found between all UC components and gestational age and fetal weight. The UCA of MCDA fetuses was significantly larger than that of DC fetuses (p < 0.001) at the expense of a larger WJA (p < 0.001) and similar to that of singleton pregnancies. The MCDA fetuses with an estimated fetal weight below the 10th percentile had a smaller UCA than fetuses with a normal estimated weight (p < 0.001). CONCLUSION: The MCDA twins exhibited a thicker UC than that of dichorionic twins.

WHO criteria for diabetes in pregnancy: a retrospective cohort.

BACKGROUND: Recognizing that hyperglycemia in pregnancy can impact both individually a patient's health and collectively the healthcare system and that different levels of hyperglycemia incur different consequences, we aimed to evaluate the differences and similarities between patients who met the diagnostic criteria for gestational diabetes mellitus (GDM) or diabetes in pregnancy (DIP) according to the World Health Organization diagnostic criteria based on the 75 g oral glucose tolerance test (OGTT). METHODS: This retrospective study included a cohort of 1064 women followed-up at the Gestational Diabetes Unit of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (Sao Paulo, Brazil). Patients were classified into GDM and DIP groups, according to their OGTT results. Their electronic charts were reviewed to obtain clinical and laboratory data for all participants. RESULTS: Women in the DIP group had a higher pre-pregnancy body mass index (30.5 vs 28.1 kg/m2, odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.11), more frequently experienced GDM in a previous pregnancy (25% vs. 11%, OR 2.71, 95% CI 1.17-6.27), and were more likely to have chronic hypertension (43.1% vs. 23.5%, OR 2.46, 95% CI 1.47-4.11), a current twin pregnancy (10.8% vs. 2.9%, OR 4.04, 95% CI 1.70-9.61), or require insulin (46.1% vs. 14.3%, OR 5.14, 95% CI 3.06-8.65) than those in the GDM group. Patients in the DIP group also had a higher frequency of large-for-gestational-age infants (12.3% vs. 5.1%, OR 2.78, 95% CI 1.23-6.27) and abnormal postpartum OGTT (45.9% vs. 12.6%, OR 5.91, 95% CI 2.93-11.90) than those in the GDM group. Nevertheless, in more than half of the DIP patients, glucose levels returned to normal after birth. CONCLUSIONS: Diabetes in pregnancy is associated with an increased risk of adverse perinatal outcomes but does not equate to a diagnosis of diabetes post-pregnancy. It is necessary to identify and monitor these women more closely during and after pregnancy. Keeping patients with hyperglycemia in pregnancy engaged in healthcare is essential for accurate diagnosis and prevention of complications related to abnormal glucose metabolism.

Association between preterm births and socioeconomic development: analysis of national data.

BACKGROUND: The increasing prevalence of preterm birth, which is a global phenomenon, is attributable to the increased medical indications, artificial gestations, and some socioeconomic factors. This study was conducted to identify whether development and equality indices are associated with the incidence of preterm birth, specifically, spontaneous and elective preterm births. METHODS: This retrospective observational study comprised an analysis of data on live births from 2019 in Brazil and on socioeconomic indices that were derived from census information in 2017. Data were summarised using absolute and relative frequencies. Spearman's correlation was used to determine the correlation between socioeconomic factors and the preterm birth rate. Multiple beta regression analysis was performed to determine the best model of socioeconomic covariates and preterm birth rate. The significance level was set at 5%. RESULTS: In 2019 in Brazil, the preterm birth rate was 11.03%, of which 58% and 42% were spontaneous and elective deliveries, respectively. For all preterm births, Spearman's correlation varied from ρ = 0.4 for the Gini Index and ρ = - 0.24 for illiteracy. The best fit modelled the spontaneous preterm birth fraction as a negative function of the Human Development Index (HDI). The best-fit model considered the expected elective preterm birth fraction as a positive function of the HDI and as a negative function of the Gini Index, which was used as a precision parameter. CONCLUSIONS: We observed a reduction in the fraction of spontaneous preterm births; however, the distribution was not uniform in the territory: higher rates of spontaneous preterm birth were noticed in the north, northeast, and mid-west regions. Thus, areas with lower education levels and inequal income distribution have a higher proportion of spontaneous preterm birth. The fraction of elective preterm birth was positively associated with more advantaged indices of socioeconomic status.

Isolation and characterization of Toxoplasma gondii isolates from human congenital toxoplasmosis cases reveal a new virulent genotype in São Paulo, Brazil.

Toxoplasma gondii causes severe disease in congenitally infected fetuses. The severity of fetal infection is related to the gestational stage at the time of maternal infection, parasite burden, and genotypic characteristics. South America has a high incidence of congenital toxoplasmosis and has the highest genotypic diversity of the parasite. In Brazil, clinical toxoplasmosis in children is notorious, however there are very limited data regarding the strains recovered from congenital infections. In this study, T. gondii strains from two cases of severe congenital toxoplasmosis from the São Paulo metropolitan area were isolated (TgHumIMTBr2 and TgHumIMTBr3) and biologically and molecularly characterized using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and microsatellite analysis, revealing a new non-archetypal virulent genotype designated as #318. The other isolate, genotype #175, has already been described in domestic and wild animals in Brazil, but is now associated with acute toxoplasmosis in humans. These data reinforce the role of non-archetypal T. gondii genotypes in the severity of human congenital toxoplasmosis, highlighting the importance of studies focused on parasite isolation and genotyping for a better understanding of the virulence of isolates from human toxoplasmosis and contributing to the knowledge of the diversity of T. gondii in Brazil.

Pre-pregnancy dietary pattern is associated with newborn size: results from ProcriAr study.

Babies born small-for-gestational age (SGA) have an increased risk of mortality, morbidity and adverse functional consequences. Studies suggest that pre-pregnancy maternal diet may influence newborns' size. This study aimed to determine whether maternal pre-pregnancy dietary patterns (DP) are associated with delivering SGA newborns in the ProcriAr Cohort Study, Sao Paulo-Brazil. Pre-pregnancy DP of 299 women were investigated using factor analysis with principal component's estimation, based on intake reported on a validated 110-item FFQ. Newborns were classified as SGA if their weight and/or length, adjusted by gestational age and sex, were below the 10th percentile of the INTERGROWTH-21st standards. Multivariate Poisson regression modelling with robust error variance was performed to examine associations between the different DP (in quintiles) and SGA. In a model adjusted by maternal sociodemographic and health behaviours, women who scored in the highest quintile of the DP 'Snacks, sandwiches, sweets and soft drinks' (in relation to the women who scored in the lowest quintile) were significantly more likely to deliver SGA babies (relative risk 1·92; 95 % CI 1·08, 3·39). This study verified that women's pre-pregnancy dietary behaviour characterised by an energy-dense nutrient-poor food intake was a risk factor for delivering SGA newborns. Investments in education and improved access to healthful food and nutritional information before pregnancy should be prioritised due to their potential positive impact on child health. However, further studies are warranted to identify specific metabolic pathways that may be underlying these associations.

Fetal gastroschisis: Maternal and fetal methylation profile.

OBJECTIVE: The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors. METHOD: Genome-wide DNA methylation analysis of 96 blood samples was performed using the Illumina Human Methylation 850K BeadChip. The blood samples were collected as follows: 32 from the umbilical cord of fetuses with gastroschisis, 32 from their respective mothers, 16 from the umbilical cord of fetuses without malformation, and 16 from their respective mothers. RESULTS: The differential DNA methylation analysis showed a significant difference between the groups. The enrichment analysis resulted in 12 sites related to T-cell activation (p = 0.0128). The sites with different methylation status contained 10 genes, three of which were related to the beta-2-microglobulin gene. The methylation profile observed in the fetuses with gastroschisis was not inherited from the mothers. In addition, there was no association between maternal urinary tract infection, smoking, and alcohol use and different methylated sites. CONCLUSION: We established the methylation profile of gastroschisis fetuses, which differs from that of normal fetuses. The profile was not inherited and did not correlate with maternal risk factors.

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

COL1A1, COL4A3, TIMP2 and TGFB1 polymorphisms in cervical insufficiency.

OBJECTIVES: To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history. METHODS: Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain (COL1A1), rs1882435 in collagen type IV alpha 3 chain (COL4A3), rs2277698 in metallopeptidase inhibitor 2 (TIMP2), and rs1800468 in transforming growth factor beta 1 (TGFB1). RESULTS: We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011). CONCLUSIONS: The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes.

Open fetal myelomeningocele repair at a university hospital: surgery and pregnancy outcomes.

PURPOSE: Myelomeningocele (MMC) is an open neural tube defect that causes great morbidity. Prenatal open repair is the standard treatment; however, there are many complications related to the procedure. This study reports preliminary findings of open in utero repair of MMC in a public tertiary hospital in Brazil and describes factors that could be associated with increased surgical morbidity. METHODS: Thirty-nine patients underwent open in utero repair of MMC from October 2015 to August 2019. The Clavien-Dindo classification of surgical complications and a classification system with the preterm definitions of the World Health Organization were used, respectively, for maternal and fetal complications. RESULTS: A total of 28 mothers (71.8%) and 31 fetuses (79.5%) experienced at least one minor to major complication. Three mothers (7.7%) had a severe grade 4 complication. Fetal complications grades 3 to 5 occurred in 13 fetuses (33.3%). Gestational age at surgery and at birth were 24.88 ± 1.16 weeks and 33.23 ± 3.68 weeks, respectively. Preterm delivery occurred in 30 patients (76.9%), membrane rupture in 18 patients (46.2%) and chorioamnionitis in 13 patients (33.3%). CONCLUSION: Open fetal surgery for MMC was performed at a Brazilian public tertiary care center, resulting in three grade 4 maternal complications. Relevant fetal complications were also present. The use of a standard classification system for complications renders studies more comparable and data more useful for counseling patients. Adjustments of perioperative procedures and long-term follow-up are needed to determine the real benefit of open in utero repair of MMC at our hospital.

Fetal-Maternal Hemorrhage in First-Trimester Intrauterine Hematoma.

OBJECTIVE: The objective of this study was to compare the frequency and percentage of fetal hemoglobin (HbF%) by flow cytometry of (1) first-trimester asymptomatic patients with intrauterine hematoma (IUH), (2) first-trimester pregnant patients with vaginal bleeding (VB), and (3) first-trimester asymptomatic pregnant women without hematoma. METHODS: Prospective study involving pregnant women in the first trimester of pregnancy. Patients with ultrasound findings of asymptomatic hematoma and with VB were paired with asymptomatic pregnant women of same gestational age without hematoma (control group [CG]). Maternal blood HbF% was evaluated by flow cytometry. The groups were compared in terms of circulating fetal hemoglobin and HbF%. RESULTS: Sixty-six patients were selected, 22 with hematoma, 17 with bleeding, and 27 in the CG. Fetal hemoglobin was detected in 15 patients with hematoma (68.2%) and 13 with bleeding (76.5%) and in 20 of the control (74.1%) (p = 0.830). The mean HbF% of each group was 0.054, 0.012, and 0.042 for hematoma, bleeding, and control, respectively, and differences were not significant (p = 0.141). There was a moderate negative correlation between the volume of hematoma and HbF% (rSpearman = -0.527; p = 0.012). CONCLUSIONS: The fetal-maternal hemorrhage expressed by Hbf% in first-trimester pregnancies did not seem to differ between patients with and without ultrasound findings of IUH.

Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility.

BACKGROUND: Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia. METHODS: In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts. FINDINGS: The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended. INTERPRETATION: We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.

Kidney impairment in fetal growth restriction: three-dimensional evaluation of volume and vascularization.

OBJECTIVES: Renal development is impaired in fetal growth restriction (FGR). Renal size can be considered a surrogate of renal function in childhood, and could be impaired in that condition. Our aim was to evaluate the ratio of total renal volume, measured by three-dimensional ultrasound, to estimated fetal weight (TRV/EFW) among fetuses with and without growth restriction. Furthermore, we correlated TRV/EFW with fetal Doppler velocimetry and renal vascularization indexes and evaluated the association of renal volume and vascular parameters with adverse neonatal events in growth-restricted fetuses. METHODS: In a retrospective cohort, TRV and renal vascularization of growth-restricted and normal fetuses were evaluated by three-dimensional ultrasonography and VOCAL technique. Independent samples t-tests and Mann-Whitney test were used for comparisons between groups. Logistic regression model was applied to evaluate the association between renal characteristics and adverse neonatal events. RESULTS: Seventy-one growth-restricted fetuses were compared to 194 controls. The TRV/EFW was lower in the growth-restricted group (P < .001). In our sample, this ratio did not correlate with Doppler velocimetry parameters, renal vascular indexes or any adverse neonatal events. CONCLUSION: The TRV/EFW ratio is decreased in FGR. Further studies are needed to investigate the association of this ratio with long-term renal outcomes.

Maternal nutrient intake and fetal gastroschisis: A case-control study.

Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of the abdominal organs. This multifactorial malformation occurs in young pregnant women, and the underlying cause of the disease remains unknown; however, nutritional factors may play a role in its development. This case-control study explored the association of maternal nutrient intake with the occurrence of gastroschisis. The gastroschisis group (GG) comprised 57 pregnant women with fetuses with gastroschisis, and the control group (CG) comprised 114 pregnant women with normal fetuses matched for maternal age, gestational age, and preconception body mass index classification. Nutritional assessments related to the preconception period were obtained using the food consumption frequency questionnaire, and nutrient intakes were calculated using nutrition programs. The median daily calorie intake was higher (2,382.43 vs. 2,198.81; p = .041) in the GG than in the CG. The median intake of methionine (763.89 vs. 906.34; p = .036) and threonine (1,248.34 vs. 1,437.01; p = .018) was lower in the GG than in the CG. Pregnant women with fetuses with gastroschisis have a diet characterized by higher calorie intake and lower levels of essential amino acids (methionine and threonine) during the preconception period than pregnant women with normal fetuses.

First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction.

BACKGROUND: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage. METHODS: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (µALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. RESULTS: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and µALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%). CONCLUSIONS: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.