Preterm births prevalence during the COVID-19 pandemic in Brazil: results from the national database.

The SARS-CoV-2 (COVID-19) pandemic impacted the health systems between and within countries, and in the course of the pandemic sexual and reproductive health services were the most disrupted. Findings from high-income settings have reported significant changes in preterm birth prevalence during the pandemic period. To understand the possible effects of the COVID-19 pandemic on preterm birth numbers at the Brazilian national level. We compare the number of preterm deliveries during the COVID-19 pandemic period (2020 and 2021) with previous years. We conducted a population-based cross-sectional study taking the period from January 2017 to December 2021 to account. We use individual-level live births data from the Brazilian Live Birth Information System (SINASC), and we estimate the odds ratio (OR) of preterm deliveries using propensity score weighting analysis in Brazil and its regions. During the study period (from 2017 to 2021), about 2.7 million live births were recorded per year, and the missing value for gestational age at delivery was less than 1.5%. The preterm birth prevalence slightly increased during the COVID-19 pandemic compared to the pre-pandemic period (11.32% in 2021 vs 11.09% in 2019, p-value < 0.0001). After adjusting for sociodemographic variables, the OR of preterm births in Brazil has significantly increased, 4% in 2020 (OR: 1.04 [1.03-1.05] 95% CI, p-value < 0.001), and 2% in 2021(OR: 1.02 [1.01-1.03] 95% CI, p-value < 0.001), compared to 2019. At the regional level, the preterm birth pattern in the South, Southeast and Northeast regions show a similar pattern. The highest odds ratio was observed in the South region (2020 vs 2019, OR: 1.07 [1.05-1.10] 95% CI; 2021 vs 2019, OR: 1.03 [1.01-1.06] 95% CI). However, we also observed a significant reduction in the ORs of preterm births in the northern region during the COVID-19 pandemic (2020 vs 2019, OR: 0.96 [0.94-0.98] 95% CI) and (2021 vs 2019, OR: 0.97 [0.95-0.99] 95% CI). Our analysis shows that the pandemic has increased regional variation in the number of preterm births in Brazil in 2020 and 2021 compared to the pre-pandemic years.

Association between cervical length and gestational age at birth in singleton pregnancies: a multicentric prospective cohort study in the Brazilian population.

BACKGROUND: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women. METHODS: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points. RESULTS: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis. CONCLUSIONS: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB.

Screening, diagnosis and management of hypothyroidism in pregnancy: Number 10 - October 2022

Key points Pregnancy places a metabolic overload on the maternal thyroid, especially in the first trimester, mainly because of the demand imposed by the conceptus. The fetal thyroid becomes functionally mature only around pregnancy week 20. Until then, the fetus depends on the transfer of maternal thyroid hormones (THs). Thyroid hormones are essential for the adequate fetal neurofunctional and cognitive development. Hypothyroidism brings higher risks of obstetric and fetal complications, namely, first-trimester miscarriage, preeclampsia and gestational hypertension, placental abruption, prematurity, low birth weight, and higher perinatal morbidity and mortality. Primary hypothyroidism (involvement of the gland with difficulty in producing and/or releasing TH) is the most common form of disease presentation, with the main etiology of Hashimoto's thyroiditis of autoimmune origin. In about 85%-90% of cases of Hashimoto's thyroiditis, antithyroid antibodies are present; the antithyroperoxidase (ATPO) is the most frequent. Positivity for ATPO is determined when circulating values exceed the upper limit of the laboratory reference. It implies greater risks of adverse maternal-fetal outcomes. Such a correlation occurs even in ranges of maternal euthyroidism. The critical point for the diagnosis of hypothyroidism during pregnancy is an elevation of thyroid-stimulating hormone (TSH). The measurement of free thyroxine (FT4) differentiates between subclinical and overt hypothyroidism. In subclinical hypothyroidism, FT4 is within the normal range, whereas in overt hypothyroidism, FT4 values are below the lower limit of the laboratory reference. Treatment of hypothyroidism is performed with levothyroxine (LT4) replacement with the aim of achieving adequate TSH levels for pregnancy. Some women have a previous diagnosis of hypothyroidism, and may or may not be compensated at the beginning of pregnancy. Even in compensated cases, the increase in LT4 dose is necessary as soon as possible. In the postpartum period, adjustment of the LT4 dose depends on the condition of previous disease, on the positivity for ATPO, and also on the value of LT4 in use at the end of pregnancy. Recommendations In places with full technical and financial conditions, TSH testing should be performed for all pregnant women (universal screening) as early as possible, ideally at the beginning of the first trimester or even in preconception planning. In places with less access to laboratory tests, screening is reserved for cases with greater risk factors for decompensation, namely: previous thyroidectomy or radioiodine therapy, type 1 diabetes mellitus or other autoimmune diseases, presence of goiter, previous history of hypo or hyperthyroidism or previous ATPO positivity. The TSH dosage should be repeated throughout pregnancy only in these cases. The diagnosis of hypothyroidism is made from the TSH value > 4.0 mIU/L. Pregnant women with previous hypothyroidism, overt hypothyroidism diagnosed during pregnancy or those with the above-mentioned higher risk factors for decompensation should be referred for risk antenatal care, preferably in conjunction with the endocrinologist. Overt hypothyroidism in pregnancy is identified when TSH > 10 mIU/L, and treatment with LT4 is readily recommended at an initial dose of 2 mcg/kg/day. TSH values > 4.0 mUI/L and ≤ 10.0 mUI/L require FT4 measurement with two diagnostic possibilities: overt hypothyroidism when FT4 levels are below the lower limit of the laboratory reference, or subclinical hypothyroidism when FT4 levels are normal. The treatment for subclinical hypothyroidism is LT4 at an initial dose of 1 mcg/kg/day, and the dose should be doubled upon diagnosis of overt hypothyroidism. In cases of TSH > 2.5 and ≤ 4.0 mIU/L, if there are complete conditions, ATPO should be measured. If positive (above the upper limit of normal), treatment with LT4 at a dose of 50 mcg/day is indicated. If conditions are not complete, the repetition of the TSH dosage should be done only for cases at higher risk. In these cases, treatment with LT4 will be established when TSH > 4.0 mIU/L at a dose of 1 mcg/kg/day; if needed, the dose can be adjusted after FT4 evaluation. Women with previous hypothyroidism should have their LT4 dose adjusted to achieve TSH < 2.5 mIU/L at preconception. As soon as they become pregnant, they need a 30% increase in LT4 as early as possible. In practice, they should double the usual dose on two days a week. Levothyroxine should be given 30-60 minutes before breakfast or three hours or more after the last meal. Concomitant intake with ferrous sulfate, calcium carbonate, aluminum hydroxide and sucralfate should be avoided. The target of LT4 therapy during pregnancy is to achieve a TSH value < 2.5 mIU/L. Once the therapy is started, monthly control must be performed until the mentioned goal is reached. In the postpartum period, women with previous disease should resume the preconception dose. Cases diagnosed during pregnancy in use of LT4 ≤ 50 mcg/day may have the medication suspended. The others should reduce the current dose by 25% to 50% and repeat the TSH measurement in six weeks. Cases of ATPO positivity are at higher risk of developing postpartum thyroiditis and de-escalation of LT4 should be performed as explained.

Perinatal Outcomes and Factors Associated with Ethnic Group in cases of Preterm Birth: the Multicenter Study on Preterm Birth in Brazil.

OBJECTIVE: To investigate the characteristics of women who had preterm birth (PTB) and related outcomes according to ethnicity. METHODS: A secondary analysis of a multicenter cross-sectional study conducted in Brazil. Women who had PTB were classified by self-report as white and non-white. Clinical, pregnancy, and maternal data were collected through postpartum interviews and reviews of medical charts. The sociodemographic, obstetric and clinical characteristics of the women, as well as the mode of delivery and the neonatal outcomes among different ethnic groups were compared through a bivariate analysis. RESULTS: Of the 4,150 women who had PTB, 2,317 (55.8%) were non-white, who were more likely: to be younger than 19 years of age (prevalence ratio [PR]: 1.05; 95% confidence interval [95%CI]: 1.01-1.09); to be without a partner; to live on low income; to have lower levels of schooling; to have ≥ 2 children; to perform strenuous work; to be from the Northeastern region of Brazil rather than the from Southern region; to have a history of ≥ 3 deliveries; to have an interpregnancy interval < 12 months; to have pregnancy complications such as abortion, PTB, preterm premature rupture of membranes (pPROM), and low birth weight; to initiate antenatal care (ANC) visits in the second or third trimesters; to have have an inadequate number of ANC visits; to be under continuous overexertion; to smoke in the first and second or third trimesters; and to have anemia and gestational hypertension. The maternal and neonatal outcomes did not differ between the groups, except for the higher rate of low birth weight (73.7% versus 69.0%) in infants born to non-white women, and the higher rate of seizures (4.05% versus 6.29%) in infants born to white women. CONCLUSION: Unfavorable conditions were more common in non-whites than in whites. Proper policies are required to decrease inequalities, especially in the context of prematurity, when women and their neonates have specific needs.

OBJETIVO: Investigar as características das mulheres com parto pré-termo e os respectivos resultados de acordo com a etnia. MéTODOS: Uma análise secundária de um estudo de corte transversal multicêntrico no Brasil. Mulheres com parto pré-termo foram classificadas por autodefinição como brancas ou não brancas. Dados maternos, clínicos, e da gestação foram coletados por entrevista pós-parto e revisão de prontuários. As características sociodemográficas, obstétricas e clínicas das mulheres, o tipo de parto, e os resultados neonatais dos grupos étnicos foram comparados por análise bivariada. RESULTADOS: Das 4.150 mulheres que tiveram parto pré-termo, 2.317 (55,8%) eram não brancas, que com mais frequência: eram menores de 19 anos de idade (razão de prevalência [RP]: 1,05; intervalo de confiança de 95% [IC95%]: 1,01­1,09); não tinham parceiro; eram de baixa renda; tinham baixa escolaridade; tinham ≥ 2 filhos; realizavam trabalho extenuante; provinham mais do Nordeste do que do Sul; tinham histórico de ≥ 3 partos; tinham intervalo interpartal < 12 meses; e tiveram complicações gestacionais como aborto, parto pré-termo, rotura prematura de membranas pré-termo (RPM-PT) e baixo peso ao nascimento; iniciaram as consultas de pré-natal no segundo ou terceiro trimestres; compareceram a um número inadequado de consultas; viviam sob contínua exaustão; fumaram no primeiro e segundo ou terceiro trimestres; e tiveram anemia e hipertensão gestacional. Os resultados maternos e neonatais não diferiram entre os grupos, exceto pela maior taxa de baixo peso ao nascimento (73,7% versus 69,0%) entre as crianças das mulheres não brancas, e e a maior taxa de convulsões (4,05% versus 6,29%) entre as das brancas. CONCLUSãO: Condições desfavoráveis foram mais comuns entre não brancas do que entre brancas. Políticas apropriadas são necessárias para diminuir as diferenças, especialmente no contexto da prematuridade, quando mulheres e seus neonatos têm necessidades específicas.

Perinatal Outcomes and Factors Associated with Ethnic Group in cases of Preterm Birth: the Multicenter Study on Preterm Birth in Brazil / Resultados perinatais e fatores associados à etnia em casos de parto pré-termo: Estudo multicêntrico de investigação de prematuridade no Brasil

Abstract Objective To investigate the characteristics of women who had preterm birth (PTB) and related outcomes according to ethnicity. Methods A secondary analysis of a multicenter cross-sectional study conducted in Brazil. Women who had PTB were classified by self-report as white and non-white. Clinical, pregnancy, and maternal data were collected through postpartum interviews and reviews of medical charts. The sociodemographic, obstetric and clinical characteristics of the women, as well as the mode of delivery and the neonatal outcomes among different ethnic groups were compared through a bivariate analysis. Results Of the 4,150 women who had PTB, 2,317 (55.8%) were non-white, who were more likely: to be younger than 19 years of age (prevalence ratio [PR]: 1.05; 95% confidence interval [95%CI]: 1.01-1.09); to be without a partner; to live on low income; to have lower levels of schooling; to have ≥ 2 children; to perform strenuous work; to be fromthe Northeastern region of Brazil rather than the from Southern region; to have a history of ≥ 3 deliveries; to have an interpregnancy interval<12 months; to have pregnancy complications such as abortion, PTB, preterm premature rupture of membranes (pPROM), and low birth weight; to initiate antenatal care (ANC) visits in the second or third trimesters; to have have an inadequate number of ANC visits; to be under continuous overexertion; to smoke in the first and second or third trimesters; and to have anemia and gestational hypertension. The maternal and neonatal outcomes did not differ between the groups, except for the higher rate of low birth weight (73.7% versus 69.0%) in infants born to non-white women, and the higher rate of seizures (4.05% versus 6.29%) in infants born to white women. Conclusion Unfavorable conditions weremore common in non-whites than inwhites. Proper policies are required to decrease inequalities, especially in the context of prematurity, when women and their neonates have specific needs.

Resumo Objetivo Investigar as características das mulheres com parto pré-termo e os respectivos resultados de acordo com a etnia. Métodos Uma análise secundária de umestudo de corte transversalmulticêntrico no Brasil. Mulheres com parto pré-termo foram classificadas por autodefinição como brancas ou não brancas. Dados maternos, clínicos, e da gestação foram coletados por entrevista pós-parto e revisão de prontuários. As características sociodemográficas, obstétricas e clínicas das mulheres, o tipo de parto, e os resultados neonatais dos grupos étnicos foram comparados por análise bivariada. Resultados Das 4.150 mulheres que tiveram parto pré-termo, 2.317 (55,8%) eram não brancas, que com mais frequência: eram menores de 19 anos de idade (razão de prevalência [RP]: 1,05; intervalo de confiança de 95% [IC95%]: 1,01-1,09); não tinham parceiro; eramde baixa renda; tinham baixa escolaridade; tinham ≥ 2 filhos; realizavam trabalho extenuante; provinhammais do Nordeste do que do Sul; tinham histórico de ≥ 3 partos; tinham intervalo interpartal<12 meses; e tiveram complicações gestacionais como aborto, parto pré-termo, rotura prematura de membranas pré-termo (RPM-PT) e baixo peso ao nascimento; iniciaram as consultas de pré-natal no segundo ou terceiro trimestres; comparecerama um número inadequado de consultas; viviam sob contínua exaustão; fumaram no primeiro e segundo ou terceiro trimestres; e tiveram anemia e hipertensão gestacional. Os resultados maternos e neonatais não diferiram entre os grupos, exceto pelamaior taxa de baixo peso ao nascimento (73,7% versus 69,0%) entre as crianças das mulheres não brancas, e e a maior taxa de convulsões (4,05% versus 6,29%) entre as das brancas. Conclusão Condições desfavoráveis foram mais comuns entre não brancas do que entre brancas. Políticas apropriadas são necessárias para diminuir as diferenças, especialmente no contexto da prematuridade, quando mulheres e seus neonatos têm necessidades específicas.

A Comprehensive Integrative Review of the Factors Associated with Spontaneous Preterm Birth, Its Prevention and Prediction, Including Metabolomic Markers.

Preterm birth is a major maternal complication that has a great impact on perinatal and neonatal health, with consequences suffered during childhood and adulthood. Little is known about its etiology and development, resulting in poor screening, prediction and preventive methods. The present integrative review discusses the current knowledge regarding some risk factors for preterm birth, the differences between screening and prediction methods, the limitations of some current preventive interventions, the importance of applying standardized concepts for exposures and outcomes, and why it is important to develop more accurate and reproducible methods to predict preterm birth. In addition, the authors introduce the concept of metabolomics and the technology involved in this technique, and discuss about how it has become a promising approach to identify biomarkers for spontaneous preterm birth.

Parto prematuro é uma complicação obstétrica de grande impacto para saúde perinatal e neonatal, tendo consequências também para a infância e a vida adulta. Pouco se sabe sobre sua etiologia e fatores determinantes, o que limita os métodos de rastreamento, predição e prevenção. Esta revisão integrativa traz a discussão sobre o conhecimento atual sobre fatores de risco para parto prematuro espontâneo, as diferenças entre métodos de rastreamento e predição, as limitações das atuais intervenções preventivas, a importância de se aplicar conceitos padronizados para exposição e desfecho na investigação de parto prematuro espontâneo, e porque é importante desenvolver métodos precisos e reprodutíveis para predizer o parto prematuro. Por fim, introduzimos o conceito de metabolômica e da tecnologia envolvida nessa técnica, e discutimos como ela tem se mostrado uma abordagem prosmissora para identificar biomarcadores associados ao parto prematuro espontâneo.

Metabolomics applied to maternal and perinatal health: a review of new frontiers with a translation potential.

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and "omics" sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent "boom" in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.

Prediction of Severe Maternal Outcome Among Pregnant and Puerperal Women in Obstetric ICU.

OBJECTIVE: World Health Organization recommends the use of maternal near miss as a tool to monitor and improve quality of obstetric care. Severe maternal outcome corresponds to the sum of maternal near miss and maternal death cases. This study was aimed at validating Acute Physiology and Chronic Health Evaluation II and IV, Simplified Acute Physiology Score III, and Sequential Organ Failure Assessment in pregnant and postpartum women in predicting severe maternal outcome. DESIGN: A retrospective cohort study. SETTING: Obstetric ICU in a tertiary care hospital in Brazil. PATIENTS: Pregnant and postpartum women admitted to the obstetric ICU during a 3-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 279 women were admitted to ICU, an admission rate of 34.6/1,000 live births, and the mortality index to severe maternal outcome (maternal death/maternal near miss + maternal death) was 7.7%. Total Sequential Organ Failure Assessment had a better overall performance than remaining scores for total hospitalizations (area under the curve, 0.86; standardized mortality ratio, 0.96; 95% CI, 0.74-1.22), for hypertensive direct causes (area under the curve, 0.81; standardized mortality ratio, 0.73; 95% CI, 0.31-1.43), and indirect causes (area under the curve, 0.89; standardized mortality ratio, 0.85; 95% CI, 0.59-1.19). The Acute Physiology and Chronic Health Evaluation II had a better overall performance than total Sequential Organ Failure Assessment for hemorrhagic causes (area under the curve, 0.75; standardized mortality ratio, 1.0; 95% CI, 0.61-1.54). CONCLUSIONS: Total Sequential Organ Failure Assessment may be used to predict severe maternal outcome in obstetric populations admitted to ICU. The Acute Physiology and Chronic Health Evaluation II may be applied to predict severe maternal outcome in hemorrhagic complications. We do not recommend Acute Physiology and Chronic Health Evaluation IV and Simplified Acute Physiology Score III for the prediction of severe maternal outcome.

Metabolomics applied to maternal and perinatal health: a review of new frontiers with a translation potential

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and "omics" sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent "boom" in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.

Exploring Epidemiological Aspects, Distribution of WHO Maternal Near Miss Criteria, and Organ Dysfunction Defined by SOFA in Cases of Severe Maternal Outcome Admitted to Obstetric ICU: A Cross-Sectional Study.

OBJECTIVE: To explore the epidemiological aspects, to describe the frequency and distribution of WHO maternal near miss (MNM) criteria and the presence of organ dysfunction and failure measured by the maximum SOFA (Sequential Organ Failure Assessment) score (SOFA max) in cases of severe maternal outcome (SMO). METHODS: In an observational cross-sectional study performed between January 2013 and December 2015, 279 pregnant or postpartum women were admitted to an obstetric ICU (intensive care unit) in Brazil. MNM, maternal death (grouped as SMO), and potentially life-threatening conditions (PLTC) were defined according to WHO criteria. For categorical variables, a descriptive analysis was carried out. Frequency and distribution of WHO criteria, organ dysfunction, or failure defined by SOFA max were performed. RESULTS: WHO criteria identified 65 SMO and 214 PLTC. Management criteria were present in 58/65 (89.2%) while 61/65 (93.8%) of SMO cases had dysfunction or failure by SOFA. CONCLUSIONS: The systematic evaluation of the organic function by SOFA max score identified the presence of organic dysfunction or failure in almost all SMO cases. Management criteria were present in all MD cases. Our results indicate the need for new studies evaluating the parameterization of the WHO laboratory criteria for values compatible with the definition of organic dysfunction by the SOFA to identify MNM.