Correction: Maternal mortality associated with COVID-19 in Brazil in 2020 and 2021: Comparison with non-pregnant women and men.

[This corrects the article DOI: 10.1371/journal.pone.0261492.].

Maternal mortality associated with COVID-19 in Brazil in 2020 and 2021: Comparison with non-pregnant women and men.

OBJECTIVE: Mortality rates of pregnant and postpartum women grew in the second COVID-19 pandemic year. Our objective is to understand this phenomenon to avoid further deaths. METHODS: We collected data from SIVEP-Gripe, a nationwide Brazilian database containing surveillance data on all severe acute respiratory syndrome caused by COVID-19, between the first notified case (February 2020) until the 17th epidemiological week of 2021. We stratified patients into maternal women (which includes pregnant and postpartum women), non-maternal women and men and divided them by time of diagnosis in two periods: first period (February to December 2020) and second period (the first 17 epidemiological weeks of 2021 before pregnant and postpartum women were vaccinated). RESULTS: During the second period, all patients had higher risk of presenting severe COVID-19 cases, but the maternal population was at a higher risk of death (OR of 2.60 CI 95%: 2.28-2.97)-almost double the risk of the two other groups. Maternal women also had a higher risk of needing intensive care, intubation and of presenting desaturation in the second period. Importantly, maternal women presented fewer comorbidities than other patient groups, suggesting that pregnancy and postpartum can be an important risk factor associated with severe COVID-19. CONCLUSION: Our results suggest that the Gama variant, which has been related to greater virulence, transmissibility and mortality rates leads to more severe cases of COVID-19 for pregnant and postpartum women.

Association between exposure to air pollution during intrauterine life and cephalic circumference of the newborn.

It has been observed that air pollution can affect newborn health due to the negative effects of pollutants on pregnancy development. However, few studies have evaluated the impact of maternal exposure to urban air pollution on head circumference (HC) at birth. Reduced head growth during pregnancy may be associated with neurocognitive deficits in childhood. The objectives of this study were to evaluate the association between maternal exposure to air pollution and HC at birth and to provide context with a systematic review to investigate this association. This was a prospective study of low-risk pregnant women living in São Paulo, Brazil. Exposure to pollutants, namely, nitrogen dioxide (NO2) and ozone (O3), was measured during each trimester using passive personal samplers. We measured newborn HC until 24 h after birth. We used multiple linear regression models to evaluate the association between pollutants and HC while controlling for known determinants of pregnancy. To perform the systematic review, four different electronic databases were searched through November 2018: CENTRAL, EMBASE, LILACS, and MEDLINE. We selected longitudinal or transversal designs associating air pollution and HC at birth. Two reviewers evaluated the inclusion criteria and risk of bias and extracted data from the included papers. Thirteen studies were selected for the systematic review. We evaluated 391 patients, and we did not observe a significant association between air pollution and HC. Regarding the systematic review, 13 studies were selected for the systematic review, 8 studies showed an inverse association between maternal exposure to pollutants and HC, 4 showed no association, and one observed a direct association. In the city of São Paulo, maternal exposure to pollutants was not significantly associated with HC at birth. The systematic review suggested an inverse association between air pollution and HC at birth.

Risk factors for gastroschisis: A case-control study in a Brazilian population.

OBJECTIVE: To evaluate risk factors associated with fetal gastroschisis. METHODS: As a secondary aim of a larger case-control study, pregnant women attending the Fetal Medicine Unit at the Department of Obstetrics and Gynecology at Hospital das Clinicas, Sao Paulo University Medical School between July 1, 2013, and July 31, 2015, were allocated into either the gastroschisis group, where the woman was carrying a fetus with gastroschisis, or the control group, where the fetus was normal. Patients in the control group were matched at study entry for maternal age, preconception body mass index and weeks of gestation. In-person interviews were conducted during pregnancy to obtain data on demographic, medical, and social characteristics; exposure to substances; pregnancy history; the presence of chronic disease, urinary tract infections (UTIs), influenza, and fever; and the occurrence of stress events between the month before the last menstrual period and the first trimester of pregnancy. RESULTS: Of 171 women included in the study, 57 were allocated to the gastroschisis group and 114 to the control group. There were significant associations between gastroschisis and maternal UTI (P=0.011), tobacco use (P=0.001), alcohol consumption (P≤0.001), and illicit drug use (P=0.012). After analysis by standard logistic regression, the remaining significant factors were UTI, tobacco use, and alcohol consumption. CONCLUSION: UTI and exposure to tobacco or alcohol just before conception and during early pregnancy were associated with an increase in the likelihood of fetal gastroschisis.

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.

Comparative analysis of Insulin-like growth factor binding protein-1, placental alpha-microglobulin-1, phenol and pH for the diagnosis of preterm premature rupture of membranes between 20 and 36 weeks.

AIM: Preterm premature rupture of membranes (PPROM) is responsible for approximately one-third of premature births worldwide, and although the diagnosis is often straightforward, this condition can still present difficulties. The purpose of this research was to compare the accuracy of several PPROM diagnostic tests. METHODS: A total of 94 pregnant women with clinical suspicion of PPROM who were between 20 and 36 weeks of pregnancy were examined by vaginal speculum, and tests were performed for phenol, pH, insulin-like growth factor binding protein-1 (IGFBP-1) and placental alpha-microglobulin-1 (PAMG-1). All patients were followed up until the diagnosis was fully defined, and a diagnosis of PROM was confirmed by a definitive evolution of the clinical symptoms (visualization of vaginal amniotic fluid or persistence of oligohydramnios). RESULTS: After excluding the cases that could not be definitively diagnosed, a good diagnostic performance of the immunochromatographic tests was observed that was superior to that of the clinical tests. Similar accuracies were observed for IGFBP-1 (98.7%) and PAMG-1 (93.9%). However, while the IGFBP-1 test differed from a vaginal pH ≥7 (88.9%) and the phenol test (85.7%), this did not occur for the PAMG-1 test. The performance of the tests was modified only by the presence of bleeding (with lower specificity rates for pH and phenol), without interference of gestational age or maternal morbidities. CONCLUSION: Immunochromatographic tests are good tools but should be used sparingly in resource-poor settings because they are expensive, and there is no significant difference between PAMG-1 and traditional tests.

Defective regression models for cure rate modeling with interval-censored data.

Regression models in survival analysis are most commonly applied for right-censored survival data. In some situations, the time to the event is not exactly observed, although it is known that the event occurred between two observed times. In practice, the moment of observation is frequently taken as the event occurrence time, and the interval-censored mechanism is ignored. We present a cure rate defective model for interval-censored event-time data. The defective distribution is characterized by a density function whose integration assumes a value less than one when the parameter domain differs from the usual domain. We use the Gompertz and inverse Gaussian defective distributions to model data containing cured elements and estimate parameters using the maximum likelihood estimation procedure. We evaluate the performance of the proposed models using Monte Carlo simulation studies. Practical relevance of the models is illustrated by applying datasets on ovarian cancer recurrence and oral lesions in children after liver transplantation, both of which were derived from studies performed at A.C. Camargo Cancer Center in São Paulo, Brazil.

Can we stratify the risk for insulin need in women diagnosed early with gestational diabetes by fasting blood glucose?

OBJECTIVE: The objective of this study is to evaluate risk factors and propose a model for the prediction of insulin requirement during the treatment of early-diagnosed gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Retrospective cohort analysis of all pregnant women who were diagnosed with GDM by abnormal fasting blood glucose at the first prenatal visit. According to the requirement for insulin therapy to achieve good glycemic control (insulin or diet group), women were compared regarding clinical and laboratory variables. The performance of these variables in predicting insulin need for GDM treatment was identified by a logistic regression model, and a nomogram was created based on the model to facilitate clinical interpretation. RESULTS: In total, 408 women were included for analysis. Among them, 135 (33%) needed insulin therapy. In the logistic regression model, maternal age, prepregnancy body mass index, fasting blood glucose (FBG) value, prior GDM, and family history of diabetes were significant independent variables for the prediction of insulin need. CONCLUSIONS: The need for insulin therapy in women with early diagnosis of GDM can be predicted by a logistic regression model, which can be converted to a clinically usable nomogram that could help to properly address follow-up strategies for GDM treatment in regions where health resources are limited.

Spontaneous prematurity in fetuses with congenital diaphragmatic hernia: a retrospective cohort study about prenatal predictive factors.

BACKGROUND: To evaluate possible predictive factors of spontaneous prematurity in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A retrospective cohort study was performed. Inclusion criteria were presence of CDH; absence of fetoscopy; absence of karyotype abnormality; maximum of one major malformation associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics Clinic of Clinicas Hospital at the University of São Paulo School of Medicine, from January 2001 to October 2014. The data were obtained through the electronic records and ultrasound system of our fetal medicine service. The following variables were analyzed: maternal age, primiparity, associated maternal diseases, smoking, previous spontaneous preterm birth, fetal malformation associated with hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic liver, invasive procedures performed, side of hernia and observed-to- expected lung to head ratio (o/e LHR). On individual analysis, variables were assessed using the Chi-square test and the Mann-Whitney test. A multiple logistic regression model was applied to select variables independently influencing the prediction of preterm delivery. A ROC curve was constructed with the significant variable, identifying the values with best sensitivity and specificity to be suggested for use in clinical practice. RESULTS: Eighty fetuses were evaluated, of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4% specificity for the cutoff of 40%. CONCLUSION: O/e LHR was the only predictor of prematurity in this sample.

Use of interval-censored survival data as an alternative to Kaplan-Meier survival curves: studies of oral lesion occurrence in liver transplants and cancer recurrence

After undergoing liver transplantation, children are susceptible to oral lesions due to immunosuppressant drugs that are needed to maintain the transplant. In this context, it is important to understand how disease characteristics and age at transplantation influence the development of these lesions. Monitoring of lesions begins after transplantation and children are usually observed by a specialist in stomatology at periodic visits. Consequently, lesion development is estimated to occur between two observed times, and this is characterized as interval-censored data. However, in clinical practice, it is common to assume the moment of observation as the time of event occurrence, thereby excluding interval-censored data. Here, we discuss the impact of excluding interval-censored mechanisms in statistical analyses by using simulation studies to consider differences in sample sizes and amplitudes between observed intervals. Then, application studies are presented which use a data set from a prospective study that was conducted to investigate oral lesions in patients after liver transplantation at the A.C.Camargo Cancer Center in Brazil between 2013 and 2016 and a data set involving recurrent ovarian cancer in patients diagnosed with high-grade serous carcinoma at the A.C.Camargo Cancer Center between 2003 and 2016 (AU)

Sonographic Markers in the Prediction of Fetal Complex Gastroschisis.

OBJECTIVE: To investigate the ultrasound (US) markers predictive of complex gastroschisis (CG), mortality, and morbidity in fetuses with gastroschisis. MATERIALS AND METHODS: This was a retrospective cohort study of 186 pregnancies with isolated fetal gastroschisis. Eight US markers were analyzed. The predictions and associations of US markers with CG, mortality, and morbidity were assessed. Combinations of US markers predictive of CG were investigated. RESULTS: Extra-abdominal bowel dilatation (EABD), intra-abdominal bowel dilatation (IABD), and polyhydramnios were predictive of CG. EABD between 25 and 28 weeks had a sensitivity of 64%, a specificity of 89%, a positive predictive value (PPV) of 56.2%, and negative predictive value (NPV) of 91.8%. The predictions of IABD were sensitivity = 26.7%, specificity = 96.7%, PPV = 61.5%, and NPV = 86.8%. The odds ratios for CG in the presence of 1 and 2 US markers, compared with the absence of a US marker, were 18.3 (95% CI, 3.83-87.64) and 73.3 (95% CI, 6.14-876), respectively. CONCLUSION: US markers predictive of CG were established. The combination of these markers increases the probability of CG.