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.

Cervical length distribution among Brazilian pregnant population and risk factors for short cervix: A multicenter cross-sectional study.

OBJECTIVE: Since there are populational differences and risk factors that influence the cervical length, the aim of the study was to construct a populational curve with measurements of the uterine cervix of pregnant women in the second trimester of pregnancy and to evaluate which variables were related to cervical length (CL) ≤25 mm. MATERIALS AND METHODS: This was a multicenter cross-sectional study performed at 17 hospitals in several regions of Brazil. From 2015 to 2019, transvaginal ultrasound scan was performed in women with singleton pregnancies at 18 0/7 to 22 6/7 weeks of gestation to measure the CL. We analyzed CL regarding its distribution and the risk factors for CL ≤25 mm using logistic regression. RESULTS: The percentage of CL ≤ 25mm was 6.67%. Shorter cervices, when measured using both straight and curve techniques, showed similar results: range 21.0-25.0 mm in straight versus 22.6-26.0 mm in curve measurement for the 5th percentile. However, the difference between the two techniques became more pronounced after the 75th percentile (range 41.0-42.0 mm straight x 43.6-45.0 mm in curve measurement). The risk factors identified for short cervix were low body mass index (BMI) (OR: 1.81 CI: 1.16-2.82), higher education (OR: 1.39 CI: 1.10-1.75) and personal history ([one prior miscarriage OR: 1.41 CI: 1.11-1.78 and ≥2 prior miscarriages OR: 1.67 CI: 1.24-2.25], preterm birth [OR: 1.70 CI: 1.12-2.59], previous low birth weight <2500 g [OR: 1.70 CI: 1.15-2.50], cervical surgery [OR: 4.33 CI: 2.58-7.27]). By contrast, obesity (OR: 0.64 CI: 0.51-0.82), living with a partner (OR: 0.76 CI: 0.61-0.95) and previous pregnancy (OR: 0.46 CI: 0.37-0.57) decreased the risk of short cervix. CONCLUSIONS: The CL distribution showed a relatively low percentage of cervix ≤25 mm. There may be populational differences in the CL distribution and this as well as the risk factors for short CL need to be considered when adopting a screening strategy for short cervix.

Pessary Plus Progesterone to Prevent Preterm Birth in Women With Short Cervixes: A Randomized Controlled Trial.

OBJECTIVE: To test the effectiveness of cervical pessary in addition to vaginal progesterone for the prevention of preterm birth in women with midpregnancy short cervixes. METHODS: We performed a multicenter, open-label, randomized controlled trial in 17 perinatal centers. Asymptomatic women with singleton or twin pregnancies and cervical lengths of 30 mm or less, measured at 18 0/7-22 6/7 weeks of gestation, were randomized to cervical pessary plus vaginal progesterone (pessary plus progesterone group) or vaginal progesterone only (progesterone-only group) (200 mg/day). Treatments were used from randomization to 36 weeks of gestation or delivery. The primary outcome was a composite of neonatal mortality and morbidity. Secondary outcomes were delivery before 37 weeks and before 34 weeks of gestation. Analysis was performed according to intention to treat. RESULTS: Between July 9, 2015, and March 29, 2019, 8,168 women were screened, of whom 475 were randomized to pessary and 461 to progesterone only. The composite perinatal outcome occurred in 19.2% (89/463) of the women in the pessary group compared with 20.9% (91/436) of the women in the progesterone-only group (adjusted risk ratio [aRR] 0.88, 95% CI 0.69-1.12). Delivery rates before 37 weeks of gestation were 29.1% compared with 31.4% (aRR 0.86, 95% CI 0.72-1.04); delivery rates before 34 weeks were 9.9% compared with 13.9% (aRR 0.66, 95% CI 0.47-0.93). Women in the pessary group had more vaginal discharge (51.6% [245/476] vs 25.4% [117/479] [P<.001]), pain (33.1% [157/476] vs 24.1% [111/479] [P=.002]), and vaginal bleeding (9.7% [46/476] vs 4.8% [22/479] [P=.004]). CONCLUSION: In asymptomatic women with short cervixes, the combination of pessary and progesterone did not decrease rates of neonatal morbidity or mortality when compared with progesterone only. CLINICAL TRIAL REGISTRATION: Brazilian Clinical Trial Registry (ReBec), UTN:U1111-1164-2636.

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.

Maternal Work and Spontaneous Preterm Birth: A Multicenter Observational Study in Brazil.

Spontaneous preterm birth (sPTB) is a major pregnancy complication involving biological, social, behavioural and environmental mechanisms. Workload, shift and intensity may play a role in the occurrence of sPTB. This analysis is aimed addressing the effect of occupational activities on the risk for sPTB and the related outcomes. We conducted a secondary analysis of the EMIP study, a Brazilian multicentre cross-sectional study. For this analysis, we included 1,280 singleton sPTB and 1,136 singleton term birth cases. Independent variables included sociodemographic characteristics, clinical complications, work characteristics, and physical effort devoted to household chores. A backward multiple logistic regression analysis was applied for a model using work characteristics, controlled by cluster sampling design. On bivariate analysis, discontinuing work during pregnancy and working until the 7th month of pregnancy were risks for premature birth while working during the 8th - 9th month of pregnancy, prolonged standing during work and doing household chores appeared to be protective against sPTB during pregnancy. Previous preterm birth, polyhydramnios, vaginal bleeding, stopping work during pregnancy, or working until the 7th month of pregnancy were risk factors in the multivariate analysis. The protective effect of variables compatible with exertion during paid work may represent a reverse causality. Nevertheless, a reduced risk associated with household duties, and working until the 8th-9th month of pregnancy support the hypothesis that some sort of physical exertion may provide actual protection against sPTB.

Perinatal outcomes from preterm and early term births in a multicenter cohort of low risk nulliparous women.

Preterm birth is the major contributor for neonatal and under-five years mortality rates and also accounts for a short- and long-term adverse consequences up to adulthood. Perinatal outcomes may vary according to lots of factors as preterm subtype, late prematurity, which account for the vast majority of cases, country and population characteristics. An under-recognition of the perinatal outcomes and its associated factors might have underpowered strategies to provide adequate care and prevent its occurrence. We aim to estimate the frequency of maternal and perinatal outcomes in women with different categories of preterm and term births, factors associated with poorer perinatal outcomes and related management interventions. A multicentre prospective cohort in five maternities in Brazil between 2015 and 2018. Nulliparous low-risk women with singletons were included. Comprehensive data were collected during three antenatal visits (at 19-21weeks, 27-29 weeks and 37-39 weeks). Maternal and perinatal outcomes were also collected according to maternal and neonatal medical records. Women who had spontaneous (sPTB) and provider-initiated (pi-PTB) preterm birth were compared to those who had term birth. Also, late preterm birth (after 34 weeks), and early term (37-38 weeks) were compared to full term birth (39-40 weeks). Bivariate analysis estimated risk ratios for maternal and adverse outcomes. Finally, a multivariate analysis was conducted to address factors independently associated with any adverse perinatal outcome (APO). In total, 1,165 women had outcome data available, from which 6.7% had sPTB, 4.0% had pi-PTB and 89.3% had a term birth. sPTB and pi-PTb were associated with poorer perinatal outcomes, as well as late sPTB, late pi-PTB and early term neonates. pi-PTB (RRadj 8.12, 95% CI [2.54-25.93], p-value 0.007), maternal weight gain between 20 and 27 weeks

Adequate Placental Sampling for the Diagnosis and Characterization of Placental Infection by Zika Virus.

The detection of Zika virus (ZIKV) in immunoprivileged anatomical sites, potential sites for viral persistence, may guide the confirmation of undefined cases of ZIKV infection and also bring to light unknown pathways of viral transmission. Thus, this study aimed to characterize ZIKV infection in stratified, standardized placental samples in women with exanthematic febrile manifestations during pregnancy and compare findings to the standard investigation protocol of official health agencies. To this end, a case series of placental findings within a prospective cohort study was conducted over a period of 24 months. Serum/urine were obtained at the time of clinical case identification. Placental sampling was performed following standard investigation protocol (samples of 1.0 cm sent to a reference laboratory) and in a systematic way at various regions, such as chorionic plate, chorionic villi, basal plate, amniotic membrane, and umbilical cord, for subsequent ZIKV identification and quantification. Clinical information was obtained and histological preparation with hematoxylin-eosin staining for morphological evaluation was performed. This case series included 17 placentas systematically collected. Of these, 14 were positive by qRT-PCR for ZIKV, 5 in the umbilical cord, 7 in the amniotic membrane, 7 in the chorionic plate, 13 in the chorionic villi, and 7 in the basal plate, whereas none were reported by the reference laboratory. The most common morphological and anatomopathological findings were increased stromal cellularity, villitis, calcification, maternal vascular malperfusion, placental hypoplasia, and maternal-fetal hemorrhage (intervillous thrombi). Seven women presented positive testing for ZIKV in serological and/or molecular tests during gestation in urine. While viral quantification in urine ranged from 101 to 103 FFU eq/ml, that in different placental regions ranged from 103 to 108 FFU eq/g. Thus, ZIKV can infect different regions of the placenta and umbilical cord of pregnant women, showing that the systematic collection and adequate storage of the placenta is fundamental for the detection of ZIKV in this organ. The detection of ZIKV in the placenta after several months of initial symptoms suggests that this tissue may be a site for viral persistence during pregnancy.

Maternal and perinatal outcomes and factors associated with twin pregnancies among preterm births: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP).

OBJECTIVE: To compare maternal and perinatal outcomes between twin and single preterm births (PTB) and associated factors. METHODS: A cross-sectional multicenter study was conducted in Brazil with 4046 PTBs from April 2011 to July 2012. Causes of PTB, use of tocolytics, corticosteroids, and antibiotics in twin and single pregnancies, and factors possibly associated with twinning were evaluated using χ2 tests. Maternal and perinatal outcomes were assessed with prevalence ratios (PR). RESULTS: The main cause of PTB in twin pregnancy was spontaneous onset of preterm labor. Tocolytics were more frequently used in twins (26.9% vs 20.2%). Factors associated with PTB in twins were: maternal age >25 years (62.3% vs 53.4%); interpregnancy interval >3 years (39.0% vs 33.4%); no history of PTB (87.4% vs 79.6%); no previous maternal conditions (78.0% vs 73.3%); no alcohol abuse (88.5% vs 84.3%); no drug addiction (97.5% vs 94.5%); and >6 prenatal visits (46.5% vs 37.6%). Twin pregnancies run a 46% higher risk of cesarean delivery, while first and second twins face a 20% higher risk of low birth weight. Twin pregnancies run increased risks for admission to the NICU, cerebral hemorrhage, necrotizing enterocolitis, and any adverse perinatal outcome. CONCLUSION: Preterm twin birth is associated with low birth weight and worse neonatal outcomes.

Clinical and epidemiological factors associated with spontaneous preterm birth: a multicentre cohort of low risk nulliparous women.

The objective of this study was to determine incidence and risk factors associated with spontaneous preterm birth (sPTB). It was a prospective multicentre cohort study performed in five Brazilian referral maternity hospitals and enrolling nulliparous women at 19-21 weeks. Comprehensive maternal data collected during three study visits were addressed as potentially associated factors for sPTB. Bivariate and multivariate analysis estimated risk ratios. The main outcomes measures were birth before 37 weeks due to spontaneous preterm labour or premature rupture of membranes (sPTB). The comparison group was comprised of women with term births (≥37weeks). Outcome data was available for 1,165 women, 6.7% of whom had sPTB, 16% had consumed alcohol and 5% had used other illicit drugs during the first half of pregnancy. Current drinking at 19-21 weeks (RR 3.96 95% CI [1.04-15.05]) and a short cervix from 18-24 weeks (RR 4.52 95% CI [1.08-19.01]) correlated with sPTB on bivariate analysis. Increased incidence of sPTB occurred in underweight women gaining weight below quartile 1 (14.8%), obese women gaining weight above quartile 3 (14.3%), women with a short cervix (<25 mm) at 18-24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the first half of pregnancy (40%). Cervical length (RRadj 4.52 95% CI [1.08-19.01]) was independently associated with sPTB. In conclusion, the incidence of sPTB increased in some maternal phenotypes, representing potential groups of interest, the focus of preventive strategies. Similarly, nulliparous women with a short cervix in the second trimester require further exploration.

A randomized controlled trial on the use of pessary plus progesterone to prevent preterm birth in women with short cervical length (P5 trial).

BACKGROUND: Preterm birth is the leading cause of mortality and disability in newborn and infants. Having a short cervix increases the risk of preterm birth, which can be accessed by a transvaginal ultrasound scan during the second trimester. In women with a short cervix, vaginal progesterone and pessary can both reduce this risk, which progesterone more established than cervical pessary. The aim of this study is to compare the use of vaginal progesterone alone versus the association of progesterone plus pessary to prevent preterm birth in women with a short cervix. METHODS: This is a pragmatic open-label randomized controlled trial that will take place in 17 health facilities in Brazil. Pregnant women will be screened for a short cervix with a transvaginal ultrasound between 18 0/7 until 22 6/7 weeks of gestational age. Women with a cervical length below or equal to 30 mm will be randomized to the combination of progesterone (200 mg) and pessary or progesterone (200 mg) alone until 36 + 0 weeks. The primary outcome will be a composite of neonatal adverse events, to be collected at 10 weeks after birth. The analysis will be by intention to treat. The sample size is 936 women, and a prespecified subgroup analysis is planned for cervical length (= < or > 25 mm). Categorical variables will be expressed as a percentage and continuous variables as mean with standard deviation. Time to delivery will be assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. DISCUSSION: In clinical practice, the combination of progesterone and pessary is common however, few studies have studied this association. The combination of treatment might act in both the biochemical and mechanical routes related to the onset of preterm birth. TRIAL REGISTRATION: Brazilian Clinical Trial Registry (ReBec) RBR-3t8prz, UTN: U1111-1164-2636, 2014/11/18.

Role of Body Mass Index and gestational weight gain on preterm birth and adverse perinatal outcomes.

The association of body mass index (BMI) and gestational weight gain (GWG) with preterm birth (PTB) remains controversial in the literature. To evaluate different maternal BMI and GWG categories, according to the initial BMI, in relation to different PTB subtypes and perinatal outcomes, we conducted a secondary analysis of a multicentre cross-sectional study, along with a nested case-control study including PTB from 20 centers in Brazil. Pre-pregnancy underweight was associated with a lower risk of provider-initiated PTB, while overweight and obesity were associated with a higher risk of provider-initiated PTB and a lower risk of spontaneous preterm birth. Insufficient gestational weight gain was associated with a higher prevalence of spontaneous PTB and preterm premature rupture of membranes. Excessive GWG correlated with a higher prevalence of provider-initiated PTB or preterm premature rupture of membranes. Irrespective of the initial BMI, the greater the rate of GWG, the higher the predicted probability of all PTB subtypes, except for spontaneous PTB in underweight women and those with normal BMI. On multivariate analysis, the initial BMI was shown to be the only factor associated with pi-PTB. Briefly, further studies evaluating the risk for PTB should consider that GWG may have a different role depending on the initial BMI and PTB subtype.

Cluster analysis identifying clinical phenotypes of preterm birth and related maternal and neonatal outcomes from the Brazilian Multicentre Study on Preterm Birth.

OBJECTIVE: To explore a conceptual framework of clinical conditions associated with preterm birth (PTB) by cluster analysis, assessing determinants for different PTB subtypes and related maternal and neonatal outcomes. METHODS: Secondary analysis of the Brazilian Multicentre Study on Preterm Birth of 33 740 births in 20 maternity hospitals between April 2011 and July 2012. In accordance with a prototype concept based on maternal, fetal, and placental conditions, an adapted k-means model and fuzzy algorithm were used to identify clusters using predefined conditions. The mains outcomes were phenotype clusters and maternal and neonatal outcomes. RESULTS: Among 4150 PTBs, three clusters of PTB phenotypes were identified: women who had PTB without any predefined conditions; women with mixed conditions; and women who had pre-eclampsia, eclampsia, HELLP syndrome and fetal growth restriction. The prevalence of different preterm subtypes differed significantly in the three clusters, varying from 80.95% of provider-initiated PTBs in cluster 3-6.62% in cluster 1 (P<0.001). Although some maternal characteristics differed among the clusters, maternal and neonatal outcomes did not. CONCLUSIONS: The analysis identified three clusters with distinct phenotypes. Women from the different clusters had different subtypes of PTB and maternal and pregnancy characteristics.

Use of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women: protocol for a systematic review and meta-analysis.

INTRODUCTION: Preterm birth (PTB) is the leading cause of neonatal mortality and short- and long-term morbidity. The aetiology and pathophysiology of spontaneous PTB (sPTB) are still unclear, which makes the identification of reliable and accurate predictor markers more difficult, particularly for unscreened or asymptomatic women. Metabolomics biomarkers have been demonstrated to be potentially accurate biomarkers for many disorders with complex mechanisms such as PTB. Therefore, we aim to perform a systematic review of metabolomics markers associated with sPTB. Our research question is 'What is the performance of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women?' METHODS AND ANALYSIS: We will focus on studies assessing metabolomics techniques for predicting sPTB in asymptomatic pregnant women. We will conduct a comprehensive systematic review of the literature from the last 10 years. Only observational cohort and case-control studies will be included. Our search strategy will be carried out by two independent reviewers, who will scan title and abstract before carrying out a full review of the article. The scientific databases to be explored include PubMed, MedLine, ScieLo, EMBASE, LILACS, Web of Science, Scopus and others. ETHICS AND DISSEMINATION: This systematic review protocol does not require ethical approval. We intend to disseminate our findings in scientific peer-reviewed journal, the Preterm SAMBA study open access website, specialists' conferences and to our funding agencies. PROSPERO REGISTRATION NUMBER: CRD42018100172.

Planning, Implementing, and Running a Multicentre Preterm Birth Study with Biobank Resources in Brazil: The Preterm SAMBA Study.

BACKGROUND: Our aim was to describe the steps in planning, implementing, and running a multicentre cohort study of maternal and perinatal health using a high-quality biobank comprised of maternal serum, plasma, and hair samples collected from five sites in Brazil. The Preterm SAMBA study, conducted by the Brazilian Network for Studies on Reproductive and Perinatal Health, was an innovative approach used to identify women at higher risk for preterm birth. It is also of great importance in the study of other maternal and perinatal complications in the context of Brazil, which is a middle-income country. METHODS: We described phases of planning, implementing, and running the Preterm SAMBA study, a multicentre Brazilian cohort study of low-risk nulliparous pregnant women, to validate a set of metabolite biomarkers for preterm birth identified in an external cohort. Procedures and strategies used to plan, implement, and maintain this multicentre preterm birth study are described in detail. Barriers and experience cited in the current narrative are not usually discussed in the scientific literature or published study protocols. RESULTS: Several barriers and strategies were identified in different phases of the Preterm SAMBA study at different levels of the study framework (steering committee; coordinating and local centres). Strategies implemented and resources used in the study are a legacy of the Brazilian Network, aimed at training collaborators in such complex settings. CONCLUSION: The Brazilian Network for Studies on Reproductive and Perinatal Health has gained some experience in conducting a multicentre cohort study using a resourceful biobank which may be helpful to other research groups and maternal/perinatal health networks that plan on employing a similar approach to a similar background.

Evaluation of prenatal corticosteroid use in spontaneous preterm labor in the Brazilian Multicenter Study on Preterm Birth (EMIP).

OBJECTIVE: To evaluate prenatal corticosteroid use in women experiencing spontaneous preterm labor and preterm delivery. METHODS: The present cross-sectional multicenter study analyzed interview data from patients attending 20 hospitals in Brazil owing to preterm delivery between April 1, 2011 and July 30, 2012. Patients were stratified based on preterm delivery occurring before 34 weeks or at 34-36+6  weeks of pregnancy, and the frequency of prenatal corticosteroid use at admission was compared. Prenatal corticosteroid use, sociodemographic data, obstetric characteristics, and neonatal outcomes were examined. RESULTS: There were 1455 preterm deliveries included in the present study; 527 (36.2%) occurred before 34 weeks of pregnancy and prenatal corticosteroids were used in 285 (54.1%) of these pregnancies. Among neonates delivered at 32-33+6  weeks, prenatal corticosteroid use was associated with lower pneumonia (P=0.026) and mortality (P=0.029) rates. Among neonates delivered at 34-36+6  weeks, prenatal corticosteroid use was associated with longer neonatal hospital admission (P<0.001), and an increased incidence of 5-minute Apgar scores below 7 (P=0.010), endotracheal intubation (P=0.042), surfactant use (P=0.006), neonatal morbidities (P=0.048), respiratory distress (P=0.048), and intraventricular hemorrhage (P=0.023). CONCLUSION: Preterm labor and late preterm delivery were associated with worse neonatal outcomes following prenatal corticosteroids. This could reflect a sub-optimal interval between administration and delivery.

Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA.

BACKGROUND: Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identify clinical and metabolite predictors for preterm birth. These innovative and unbiased techniques might be a strategic key to advance spontaneous preterm birth prediction. METHODS/DESIGN: Preterm SAMBA study consists of a discovery phase to identify biophysical and untargeted metabolomics from blood and hair samples associated with preterm birth, plus a validation phase to evaluate the performance of the predictive modelling. The first phase, a case-control study, will randomly select 100 women who had a spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an international consortium aimed to identify potential metabolomic predictors using biophysical data and blood samples collected at 20 weeks of gestation. The validation phase will recruit 1150 Brazilian pregnant women from five participant centres and will collect blood and hair samples at 20 weeks of gestation to evaluate the performance of the algorithm model (sensitivity, specificity, predictive values and likelihood ratios) in predicting spontaneous preterm birth (before 34 weeks, with a secondary analysis of delivery before 37 weeks). DISCUSSION: The Preterm SAMBA study intends to step forward on preterm birth prediction using metabolomics techniques, and accurate protocols for sample collection among multi-ethnic populations. The use of metabolomics in medical science research is innovative and promises to provide solutions for disorders with multiple complex underlying determinants such as spontaneous preterm birth.

The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP).

BACKGROUND: About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. METHODS AND FINDINGS: This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02-13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57-35.88), multiple pregnancy (OR 12.49; 4.86-32.05), and chronic diabetes (OR 5.24; 2.68-10.25) were the most significant factors independently associated with pi-PTB. CONCLUSIONS: pi-PTB is responsible for about one-third of all preterm births, requiring special attention. The decision-making process relative to the choice of provider-initiated birth is complex, and many factors should be elucidated to improve strategies for its prevention, including evidence-based guidelines on proper management of the corresponding clinical conditions.

Methodological issues on planning and running the Brazilian Multicenter Study on Preterm Birth.

OBJECTIVES: Assuming that the occurrence of preterm births and their maternal and neonatal associated conditions in Brazil are not completely known, a multicenter study was proposed. The purpose of this paper is to describe the methods used, its processes, achievements, and challenges. STUDY DESIGN: A multicenter cross-sectional study on preterm births in Brazilian facilities plus a nested case-control study to assess their associated factors. A description of all steps of planning and implementing such a nationwide study, including strategies for dealing with problems arising during the process, is presented. RESULTS: 20 referral hospitals in different regions of Brazil participated in the study. A detailed questionnaire for data collection, an electronic platform for data transcription and monitoring, research materials, and specific monitoring tools were developed; then data management and analyses were performed. Finally, we got information on 4,150 preterm births and 1,146 term births. CONCLUSIONS: This study represented the first step of a planned comprehensive assessment of preterm birth in Brazil, with detailed information that will lead to several analyses and further studies, bringing the knowledge to improve screening, diagnosis, and treatment practices in maternal and perinatal health with the final purpose of reducing the burden of this condition in the country.

Association between educational level and access to safe abortion in a Brazilian population.

OBJECTIVE: To evaluate sociodemographic factors associated with induced abortion. METHODS: As part of a cross-sectional, descriptive study, 15 800 civil servants from Campinas, Brazil, were invited to complete a self-administered questionnaire about absolutely unwanted pregnancies in January 2010. Bivariate analysis and multivariate Poisson regression analysis were used to explore the associations between induced abortion and sociodemographic characteristics. RESULTS: Overall, 1660 questionnaires were returned. Unwanted pregnancy was reported by 296 (17.8%) respondents, of whom 165 (55.7%) resorted to abortion. Multiple regression analysis showed that college education was the only variable associated with an increased chance of abortion. Among 157 participants who answered questions about the abortion procedure, 97 (61.8%) reported that it had been performed by a physician. Following abortion, 35 (22.9%) of 153 reported that medical care was required and 26 (16.6%) of 157 reported hospitalization, principally those with a lower level of education and those whose abortion had been performed by a nonphysician. CONCLUSION: Compared with women with a college education, those with a lower education level were less likely to terminate an absolutely unwanted pregnancy and to have an abortion performed by a physician, and they were more likely to have complications. These findings confirm the social inequalities associated with abortion in Brazil.

Brazilian multicentre study on preterm birth (EMIP): prevalence and factors associated with spontaneous preterm birth.

BACKGROUND: Preterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births. METHODS AND FINDINGS: This was a multicentre cross sectional study on preterm births in 20 referral obstetric hospitals with a case-control component to identify factors associated with spontaneous preterm birth. Surveillance was implemented at all centres to identify preterm births. For eligible consenting women, data were collected through a post-delivery questionnaire completed with information from all mother-newborn medical records until death or discharge or at a maximum of 60 days post-delivery, whichever came first. The risk of spontaneous preterm birth was estimated with OR and 95%CI for several predictors. A non-conditional logistic regression analysis was then performed to identify independently associated factors. The overall prevalence of preterm birth was 12.3%. Among them, 64.6% were spontaneous and 35.4% therapeutic. In the case-control component, 2,682 spontaneous preterm births were compared to a sample of 1,146 term births. Multivariate analyses identified the following as risk factors for spontaneous preterm birth among women with at least one previous birth: a previous preterm birth (ORadj = 3.19, 2.30-4.43), multiple pregnancy (ORadj = 29.06, 8.43-100.2), cervical insufficiency (ORadj = 2.93, 1.07-8.05), foetal malformation (ORadj = 2.63, 1.43-4.85), polyhydramnios (ORadj = 2.30, 1.17-4.54), vaginal bleeding (ORadj = 2.16, 1.50-3.11), and previous abortion (ORadj = 1.39, 1.08-1.78). High BMI (ORadj = 0.94, 0.91-0.97) and weight gain during gestation (ORadj = 0.92, 0.89-0.95) were found to be protective factors. CONCLUSIONS: The preterm birth rate in these health facilities in Brazil is high and spontaneous preterm births account for two thirds of them. A better understanding of the factors associated with spontaneous preterm birth is of utmost importance for planning effective measures to reduce the burden of its increasing rates.