FACULDADE DE MEDICINA DE RIBEIRÃO PRETO DA UNIVERSIDADE DE SÃO PAULO

Apresentação em tema: "FACULDADE DE MEDICINA DE RIBEIRÃO PRETO DA UNIVERSIDADE DE SÃO PAULO"— Transcrição da apresentação:

1 FACULDADE DE MEDICINA DE RIBEIRÃO PRETO DA UNIVERSIDADE DE SÃO PAULO
PREMATURIDADE O que fazer? São Luís 05 a 06 de agosto de 2010

2 Parto pré-termo: ocorre entre 22ª e a 37ª semana de gestação
PREMATURIDADE Parto pré-termo: ocorre entre 22ª e a 37ª semana de gestação Pré-termo tardio: entre 34 e 36 semanas Pré-termo moderado: entre 32 e 34 semanas Pré-termo extremo: antes de 32 semanas 71% RNPT Establishing definitions to understand how prematurity is often presented in the medical literature is an important starting point. A full-term pregnancy lasts 40 weeks or 280 days after the 1st day of the last normal menstrual period, or 267 days after conception. An infant born after 37 completed menstrual weeks of pregnancy, or 35 or more weeks after conception, is said to be born “at term.” Menstrual rather than conceptional age is the norm used worldwide. A preterm or premature infant is any infant born before 37 completed weeks of gestation, regardless of its birth weight. More recently, a category describing the “late preterm” infant has appeared in the medical literature. These infants are commonly identified as between 34 to 36 weeks gestation and may also be referred to as “near-term” infants. This category comprises approximately 71 percent of all preterm births in the U.S. and accounts for the majority of the increase occurring in preterm birth rates over the past two decades. Sources: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Creasy RK, Resnik R, Iams JD, eds. Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004; Davidoff MJ, Dias T, Damus K, et al. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to Semin Perinatol 2006;30:8-15. Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004; Davidoff MJ et al. Semin Perinatol 2006;30:8-15.

3 CONCEITOS Baixo peso ao nascer (BPN) Restrição crescimento intra-útero
7,6% PT 92,1% NV <2500 gramas RN muito baixo peso: peso < 1500 gramas RN extremo baixo peso: peso < 1000 gramas 63,9%PT 7,2% NV 99,3% PT 0,7% NV Restrição crescimento intra-útero Peso fetal abaixo P 10 Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004 National Center for Health Statistics, 2003 natality file.

4 IDADE GESTACIONAL PARTOS PRÉ-TERMO
71% PPT 34sem - 36sem (36s) (35s) (<32s) Seventy-one percent of preterm births in the U.S. occur after the 34th and before the 37th week of gestation. These are the “late preterm” infants. As mentioned previously, this population of preterm births has experienced a significant increase in rate over the past two decades. Births occurring before 32 weeks account for the majority of perinatal mortality and morbidity. These rates have remained relatively stable over time as seen in the next slide. Source: Davidoff MJ, Dias T, Damus K, et al. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to Semin Perinatol 2006;30:8-15. (34s) (32s) (33s) Source: National Center for Health Statistics, 2003 natality file.

5 PREMATURIDADE 1ª causa de mortalidade neonatal (<28 dias)
2ª causa de mortalidade infantil (<1 ano) 1ª causa de mortalidade infantil em crianças negras americanas Prematurity is the leading cause of neonatal mortality (deaths from birth to 28 days of life) for all infants and the number one cause of infant mortality (deaths from birth to 1 year of age) for non-Hispanic black infants in the United States. Sources: Mathews TJ, MacDorman MF. Infant mortality statistics from the 2003 period linked birth/infant death data set. Natl Vital Stat Rep 2006;54:1-29; National Center for Health Statistics, 2003 period linked birth/infant death data. Prepared by March of Dimes Perinatal Data Center, 2006. Mathews TJ, MacDorman MF. Natl Vital Stat Rep 2006;54:1-29; National Center for Health Statistics, 2003 period- linked birth/infant death data.

6 Mortalidade Perinatal & Idade Gestacional
The likelihood of perinatal death decreases substantially as the gestational age at birth increases, especially between 24 and 28 weeks of gestation. The data in this slide comes from a population-based cohort of 8,523 infants born in in Memphis (Mercer BM, 2003) and is typical of national data. Preterm infants born before 32 weeks have a substantially increased risk of long-term disability and death: 19 percent of infants born before 32 weeks die within the first year of life, compared with 1 percent of infants born at 32–36 weeks, and 0.2 percent of infants delivered at 37–41 weeks (Mathews TJ, MacDorman MF, 2006). Sources: Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:178-93; Mathews TJ, MacDorman MF. Infant mortality statistics from the 2003 period linked birth/infant death data set. National vital statistics reports; vol 54 no 16. Hyattsville, MD: National Center for Health Statistics, 2006. Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:

7 Morbidade Perinatal & Idade Gestacional
Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101: Perinatal morbidity declines rapidly between 26 and 30 weeks. Intraventricular hemorrhage, one of the most feared complications of premature birth, occurs rarely in infants born after 32 weeks of gestation following maturation of the germinal matrix in the ventricles in the brain. This slide is also from the population-based cohort of 8,523 infants born in in Memphis mentioned in slide 23. Source: Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:

8 Duração média internação hospitalar recém-nascidos
Dias 24.2 13.6 This graph clearly depicts the effect that a diagnosis of premature birth and/or low birthweight has on the average length of hospitalization for a newborn infant in the U.S. The average length of stay for an uncomplicated newborn delivery is 2 days compared to approximately 14 days for an infant with any diagnosis of prematurity and 24 days to newborns whose primary diagnosis is prematurity/low birthweight. The economic impact of the increased length of stay is enormous. 2.0 RN sem intercorrência Qq diagnóstico prematuridade/BPN Principal diagnóstico prematuridade/BPN Agency for Healthcare Research and Quality, Nationwide Inpatient Sample.

9 Consequências Econômicas da prematuridade
Custos hospitalares RN pré-termo1: $18,1 bilhões Todos RN, RNPT responsáveis por metade dos custos hospitalares ($36,7 bilhões) O custo médio internação RNPT (prolongada) 2: $77000, RN sem complicações: $1700 The costs of a preterm birth are incurred not only in the hospital’s neonatal intensive care unit. Some health problems that develop there can persist for years. 1Qq diagnóstico de prematuridade ou BPN 2 Principal diagnóstico prematuridade Agency for Healthcare Research and Quality, 2003 Nationwide Inpatient Sample.

10 Custos da prematuridade médio e longo prazo
Serviço de saúde: seguimento Educação especial: dificuldade de aprendizagem Serviço Social This slide identifies the various sources for additional long-term care costs associated with premature and low-birthweight (LBW) infants. Economic studies examining the long-term care costs of premature infants are limited. In a 2001 review article by Petrou et al., the authors examined the existing literature and provided some long-term care cost estimates associated with premature and low-birthweight infants. The authors categorized costs and economic consequences related to health care, education, social services and out-of-pocket expenses following the infants’ initial discharge from the neonatal unit. While they acknowledge the differing methodologies used in studies, the review showed higher long-term care costs for preterm or LBW compared to term infants. The authors also note that some studies were based on British cohorts and may not be generalizable to infants born in the U.S. health-care system. A more recent study in England compared the “mean societal costs” of 241 preterm children (20-25 weeks of gestation) against 160 term children during their sixth year after birth. The authors linked unit costs associated with use of health, social and other services or resources for each child during a 12-month period and found a statistically significant higher mean cost difference of $10,600 (converted to U.S. dollars) per preterm child. Again, one of the authors’ conclusions was that extreme preterm birth was “a strong predictor of high societal costs” (Petrou S et al., 2006). Sources: Petrou S, Sach T, Davidson L. The long-term costs of preterm birth and low birth weight: results of a systematic review. Child Care Health Dev. 2001;27:97-115; Petrou S, Henderson J, Bracewell M et al. Pushing the boundaries of viability: the economic impact of extreme preterm birth. Early Hum Dev. 2006;82:77-84. Custos emocionais e familiares Petrou S et al. Child Care Health Dev. 2001;27:97-115; Petrou S et al. Early Hum Dev. 2006;82:77-84.

11 INCIDÊNCIA DE PARTO PRÉ-TERMO
Tipo de população estudada Qualidade assistência pré-natal Características instituição pesquisa Variações 5 a 28% Países desenvolvidos: 6 a 8% (EUA: 12%) América Latina -Brasil: 11% (América Latina: 10 a 43%) -Chile: 4,6% CLAP,1989 Incidência se mantém há 30 anos (Challis, 2000 e 2001)

12 INCIDÊNCIA PARTO PRÉ-TERMO USA, 1983-2003
National Center for Health Statistics, 2003 final natality data. % Despite increased efforts to reduce the rate of preterm birth over the past 30 years, the rate has actually increased by 28 percent since This increase is explained only in part by the rising number of multiple gestations. Other factors include a rise in pregnancies in older women, who along with women under 20 years of age, have an increased risk of preterm birth, as seen on the next slide. Healthy People Objective Aumento 28%

13 INCIDÊNCIA PREMATURIDADE
HC-FMRP-USP: < 37sem: ,9% • 32sem a 36/6: ,7% • 22sem a 32sem: ,2% Brasil: 7% PPT foram responsáveis por 76,9% das mortes neonatais Brenelli,1989

14 Intercorrência obstétrica frequente e complexa
PARTO PRÉ-TERMO Intercorrência obstétrica frequente e complexa Contribuição Genética Influência ambiental Interações gênica-ambiental Before we begin our discussion of morbidity and mortality, we pause and note that preterm birth as a pregnancy outcome is a common, complex disorder. This requires a paradigm shift from conceptualizing adverse pregnancy outcomes as acute events caused by environmental triggers, to a view of most adverse pregnancy outcomes being like chronic conditions – resulting from the action of environmental factors on varying genetic backgrounds. Additionally, environmental factors can affect women throughout their whole life to set the stage for their pregnancy experience. And while we are not able to modify our genetic makeup, it can reveal something about susceptibility and, ultimately, help us understand how to modify the environmental factors that influence preterm birth. Lockwppd, CJ; Kuczynski, E: Markers of risk for preterm delivery. J Perinat Med 1999; 27:5-20

15 FISIOPATOLOGIA DO PARTO PRÉ-TERMO
Lockwood CL., 2002. Ativação do Eixo Materno-Fetal HHA (30%) Inflamação (40%) Hemorragia Decidual (20%) Distensão Patológica Uterina (10%) • Infecção: - Corion-Decidual - Sistemica descolamento • Gestação múltipla • Polihidramnios Anormalidade Uterina • Estresse Materno-Fetal • Liberação prematura iniciadores fisiológicos Trombina Trombina Rc Ils, TNF Estiramento mecânico Gap jct PG sintetase Receptores Ocitocina CRH E1-E3 Cório Decidua + CRH + proteases uterotoninas This diagram emphasizes the interactions among the four basic pathways to preterm contraction, membrane rupture, and cervical effacement and ripening (readiness for labor). Few, if any, preterm births follow only a single pathway. Each of these pathways are discussed in detail in the section “Pathophysiologic Pathways to Preterm Birth.” HPA = hypothalamic-pituitary-adrenal axis CRH = corticotropin-releasing hormone E1, E2, E3 = estrone, estradiol, estriol ILs = interleukens FasL = fas ligand TNF = tumor necrosis factor PG = prostaglandin Gap jct = gap junction PROM = premature rupture of membranes PTD = preterm delivery RUPREMA Contrações Uterinas Modificações Cervicais PTT

16 Inflamação Amniocoriônica-decidual e sistêmica
Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Copyright 1999 by Walter de Gruyter and Company. . DST Vaginose Bacteriana Infecção urinária •BA •Pielonefrite Pneumonia Peritonite Doença Periodontal Inflamação Amniocoriônica-decidual e sistêmica TNα/IL-1β IL-6 CRH Uterotoninas (PG, endotelina) + FasL IL-8, MMP Proteases/apoptose This figure demonstrates how inflammation activates the cytokine network, leading to uterine contractions, cervical changes, and/or rupture of the fetal membranes. CRH = corticotropin-releasing hormone IL = interleukin FasL = fas ligand TNF = tumor necrosis factor PG = prostaglandin Source: Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Contrações uterinas Ruptura das membranas Modificações cervicais

17 FATORES DE RISCO PARA TPPT
INFECÇÕES Trato Urinário, Intra-amniótica, Vulvovaginite Doença periodontal (Kirschbaum, 1993; Ovalle & Levancini, 2001; Gibbs, 2001; Offenbacher et al, 2001; Haram et al, 2003; Myers, 2004)

18 INFLAMAÇÃO, PARTO PRÉ-TERMO & RESULTADO NEONATAL
Iams JD., 2003. Factores Pró- Inflamatórios Maternos Agente microbiológico Normal Resposta Fetal Morbidade e Mortalidade Neonatal Factores Anti- Inflamatórios Maternos Morbidade Longo-prazo Resposta Materna This figure illustrates the role of infection in the maternal-fetal environment leading to preterm birth. Neonatal outcomes vary, ranging from the birth of a normal newborn to neonatal death and are largely dependent on the immunologic resistance or susceptibility of the maternal-fetal unit and its response to infection. Source: Iams JD, unpublished figure, 2003. Idade Gestational 

19 Ativação do eixo materno-fetal Hipotálamo-Hipófise-Adrenal (HHA): papel CRH
Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Copyright 1999 by Walter de Gruyter and Company. Eixo materna/Fetal HHA glicocorticoide placenta/membranas/decídua CRH + CRH-BP PGs + The first mechanism involves CRH-mediated pituitary adrenocorticotropin (ACTH) secretion in both the maternal and fetal pathways, which in turn increases maternal and fetal adrenal cortisol secretion. Increased cortisol levels cause enhanced placental CRH production and a fall in CRH binding protein, resulting in a rapid increase in circulating CRH. The elevated CRH levels cause prostaglandin production. Prostaglandins act as direct uterotonins and enhance myometrial receptivity by increasing oxytocin receptors and the formation of gap junctions. Prostaglandin-mediated cervical changes, softening and dilation, occur as a direct result. Prostaglandins, in turn, will also stimulate CRH release in placental, fetal membrane, and decidual cells, creating a positive feedback loop that enhances the preterm labor process. HPA = hypothalamic-pituitary-adrenal CRH = corticotropin-releasing hormone CRH-BP = corticotropin-releasing hormone binding protein PGs = prostaglandins Sources: Lockwood CJ. Predicting premature delivery–no easy task. N Engl J Med 2002;346:282-4; Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Contrações uterinas Ruptura das membranas Modificações cervicais

20 Ativação Eixo Fetal HHA
Ativação do eixo materno-fetal Hipotálamo-Hipófise-Adrenal (HHA): papel estrógenos e cortisol Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Copyright 1999 by Walter de Gruyter and Company. Ativação Eixo Fetal HHA Circulação UP anormal Início precoce iniciadores fisiológicos ACTH Adrenal cortisol DHEA/16-OH DHEA Placenta, Decidua Fetal Membrane Placenta ? membranes CRH E1-E3 PG + Myometrial oxytocin receptors, gap jct, MLCK calmodulin, PG synthase Estresse Materno psico-físico Violência Doméstica Estresse psicológico Fetal Fluxo uteroplacentário alterado Doenças Placenta The second mechanism, presented on the right side of the diagram, shows that CRH also stimulates the secretion of DHEA sulfate from the fetal adrenal gland which is the precursor to placental estrogen production. Estrogens interact with the myometrium to enhance gap junction formation, oxytocin receptors, and prostaglandin activity, leading to contractions and cervical changes. UPV = uteroplacental vascular HPA = hypothalamic-pituitary-adrenal ACTH = adrenocorticotropin CRH = corticotropin-releasing hormone PG = prostaglandin DHEA = dehydroepiandrosterone E1, E2, E3 = estrone, estradiol, estriol Gap jct = gap junction MLCK = myosin light chain kinases Sources: Lockwood CJ. Predicting premature delivery–no easy task. N Engl J Med 2002;346:282-4; Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Contrações uterinas Modificações cervicais Ruptura das membranas

21 HEMORRAGIA DECIDUAL Hemorragia decidual coágulo
Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Copyright 1999 by Walter de Gruyter and Company. . Hemorragia decidual Descolamento Placentário Grávidas fumantes Grávidas uso cocaína HAC+PE Trauma Materno RCIU Coagulopatias hereditárias Liberação fatores coagulação FVIIa/TF FXa Trombina uPA + tPA coágulo plasmina Active MMPs Decidual hemorrhage activates a proteolytic cascade, leading to uterine contractions, cervical changes, and/or rupture of fetal membranes. FVIIa = factor VIIa (clotting cofactor) TF = tissue factor FXa = factor Xa (clotting cofactor) uPA = urokinase-type plasminogen activator tPA = tissue-type plasminogen activator MMPs = metallomatrix proteinases ECM = extracellular matrix Source: Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. ECM Degradation Contrações uterinas Modificações cervicais Ruptura das membranas

22 FATORES DE RISCO PARA TPPT
COMPORTAMENTAIS Tabagismo: vezes risco PPT (Wisborg et al, 1996) PPT 26,7% fumantes e 18,5% não fumantes (RR 1,4 – 1,1 a 1,9) Gupta & Sreevidya, 2004 Drogas ilícitas EV (Fulroth et al, 1999; Ionnannidis et al, 2003) Má nutrição (Wildschut, 1994; Bendich, 2001; Olsen, 2002) Exercício ou trabalho físico excessivo, estresse, violência doméstica (Kramer et al, 2001; Spencer & Logan, 2002)

23 Distensão uterina anormal
Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20. Copyright 1999 by Walter de Gruyter and Company. Gestação múltipla Polihidramnios Anomalia uterina distensão uterina Capacidade expansão uterina Ativação miometrial  Contrações uterinas Modificações cervicais Ruptura das membranas Ativação citocinas membranas fetais Overdistension or decreased expansile capacity of the uterus leads to activation of the cytokine network and/or activation of the myometrium, leading to uterine contractions, cervical changes and/or rupture of the fetal membranes. Source: Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20.

24 PREMATURIDADE E GESTAÇÃO MÚLTIPLA
Source: National Center for Health Statistics, 2003 final natality data. Gibson et al, 2004 % While 1 in 10 singleton births are preterm, almost 60 percent of twins and over 90 percent of higher order multiples (triplets, quadruplets, etc.) are born prematurely. More women are having twins and triplets — whether spontaneously, as is associated with pregnancy at an older age, or more importantly in the past decade through infertility management, including use of fertility drugs and assisted reproductive technology. A major portion of the increase in the U.S. rate of preterm birth has been attributed to the increasing rates of these very high-risk multifetal pregnancies. Source: Personal communication, Dr. Roger Newman, Director of Research and Professor of Obstetrics and Gynecology, Medical University of South Carolina. Trigemelar ou mais Feto único Gemelar

25 Eventos finais no TPPT Elevação das uterotoninas
Prostaglandinas Endotelina Ocitocina Elevação na expressão proteases Matrix metaloproteinases (MMP-1/MMP-9) Ativador de Plasminogênio Plasmina Elastase Although each of the pathogenic pathways have distinct epidemiologic, clinical, biochemical and biophysical characteristics, each converges on a common pathway that results in increased uterotonins. This causes uterine contractions and an increased expression of proteases that are responsible for the breakdown of the structures of the fetal membranes and the cervix, leading to PPROM and cervical dilation. Source: Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999;27:5-20.

26 PREMATURIDADE E IDADE MATERNA
Source: National Center for Health Statistics, 2003 final natality data. % More women over age 35 are having children, and the rate of preterm birth is increased for women at both ends of the reproductive age spectrum. However, the rate of teen births (15-19 years) has declined by 33 percent since 1991, while the overall rate of preterm births has risen over the past decade, indicating that older mothers have contributed more to the rise in preterm birth rates than teens.

27 PARTO PRÉ-TERMO E RAÇA/ETNIA MATERNA USA, 1993-2003
% This slide shows the national preterm rates among singleton births contrasting Hispanic, non-Hispanic white and non-Hispanic black maternal ethnicity. African-American women are about twice as likely to deliver preterm compared to white women and represent a population with the largest disparity in preterm birth rates. Over the past decade, the decrease in the rates of preterm births among African-Americans and the increase in the rates among whites have reduced the disparity in preterm births between racial and ethnic populations; however, this is not a desirable trend to attain health equity, and the disparity in rates between many ethnic groups continues to be significant. The decreasing trend for preterm birth was disrupted when the rates for African-Americans increased from 17.4 percent in 2000 to 17.7 percent in The factors contributing to these changes in the preterm rates for African-Americans have not been clearly identified. Further investigation and research to identify and understand the causes are needed. The increase in the rate for white women is hypothesized to be a result of advanced maternal age, infertility management and multiple births. NH = non-Hispanic National Center for Health Statistics, final natality data.

28 FATORES DE RISCO PARA TPPT
Pré-gestacionais: história obstétrica PPT anterior Lazar et al,1984 – Risco de PPT • Parto anterior a termo: 5% • Parto anterior PT: 15% • 1o parto AT e 2o PPT: 24% • 1o PPT e 2o PPT: 32% Carr-Hill & Hall,1985 • 1o PPT e 2o PPT: 70%

29 Parto pré-termo anterior
Estudo coorte — Georgia 1980 a 1995 mulheres brancas e mulheres negras ● Das mulheres brancas 1º PPT (20ª- 31ªs) ● 2º PPT entre 20-31s: 8,2% ● 2º PPT entre s: 20,1% ● Total PPT (< 36s): 28,3% ● Das mulheres negras 1º PPT (20ª- 31ªs) ● 2º PPT entre 20-31s: 13,4% ● 2º PPT entre s: 23,4% ● Total PPT (< 36s): 36,8% This data from Georgia is consistent with the report 20 years earlier from Norway in showing an increased risk of preterm birth among women with a prior preterm birth. Note the higher risk of recurrence reported in black women. Source: Adams MM, Elam-Evans LD, Wilson HG, Gilbertz DA. Rates of and factors associated with recurrence of preterm delivery. JAMA 2000;283: Adams MM et al. JAMA 2000;283:

30 CLASSIFICAÇÃO DO PARTO PRÉ-TERMO
Quais são as condições que levam ao TPPT? Espontâneo - 75% ● TPPT ● RUPREMA ● Gravidez múltipla ● IIC Spontaneous preterm births follow preterm labor, preterm premature rupture of membranes (PPROM), multiple gestations, cervical insufficiency, or other related diagnoses. They account for about three-quarters of preterm births in the U.S. annually. Indicated preterm deliveries follow medical or obstetric disorders that place the mother and/or fetus at risk such as maternal hypertension, diabetes, placenta previa or abruption, and intrauterine growth restriction. These preterm births account for about one-quarter of births occurring before 37 weeks. Sources: Goldenberg RL, Iams JD, Mercer BM, et al. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network. Am J Public Health 1998;88:233-8; Meis PJ, Michielutte R, Peters TJ, et al. Factors associated with preterm birth in Cardiff, Wales. II. Indicated and spontaneous preterm birth. Am J Obstet Gynecol 1995;173: ; Meis PJ, Goldenberg RL, Mercer BM, et al. The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Am J Obstet Gynecol 1998;178:562-7. Indicação clínica (PPT terapêutico) - 25% ● Mãe e/ou feto estão em risco Goldenberg RL et al. Am J Public Health 1998;88:233-8; Meis PJ et al. Am J Obstet Gynecol 1995;173: ; Meis PJ et al. Am J Obstet Gynecol 1998;178:562-7.

31 PARTO PRÉ-TERMO ESPONTÂNEO
Apresentações Clínicas ●TPPT: % ● RUPREMA: 40-50% Fatores de risco similares: PPT anterior, fumantes, sangramento 2º trimestre e baixo nível sócio econômico, gemelar About half of women who present with either preterm labor or preterm premature rupture of membranes (PPROM) have one or more risk factors, but half do not. Risk factors associated with spontaneous preterm birth include genital tract infection, non-white race, multiple gestation, 2nd trimester bleeding, low pre-pregnancy weight, and a history of previous preterm birth. Maternal smoking and bleeding in the second trimester are particularly associated with PPROM. Sources: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Creasy RK, Resnik R, Iams JD, eds. Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004. 50% DAS PACIENTES NÃO APRESENTAM FATORES DE RISCO Goldenberg RL et al. Am J Public Health 1998;88:233-8; Meis PJ et al. Am J Obstet Gynecol 1995;173: ; Meis PJ et al. Am J Obstet Gynecol 1998;178:562-7.

32 Diagnóstico e Tocólise Assistência ao parto pré-termo
DESAFIO ESTRATÉGIAS PRIMÁRIAS Predição e Prevenção ESTRATÉGIAS SECUNDÁRIAS Diagnóstico e Tocólise ESTRATÉGIAS TERCIÁRIAS Assistência ao parto pré-termo

33 Qualidade da assistência pré-natal
PREDIÇÃO TPPT Análise de fatores de risco Registro alterações evolução gravidez Qualidade da assistência pré-natal Marcadores ● Bioquímicos ● Ultra-som

34 PREDIÇÃO TPPT Marcadores bioquímicos Fibronectina, Citocinas, CRH,
FIBRONECTINA: Faron et al, 1998 metanálise 28 trabalhos Glicoproteína conteúdo cérvico-vaginal (22ª e 36ªs) associa-se PPT pacientes alto e baixo risco Elevado VPN (81 a 96%) Pacientes alto risco PPT: resultado negativo associou-se redução risco PPT (OR 0,4; IC 95% 0,3 a 0,5) Fibronectina, Citocinas, CRH, Estrógeno salivar, Colagenase sérica, Lactoferrina,  HCG

35 PREDIÇÃO TPPT Marcador ultra-sonográfico
Comprimento do colo uterino: USTV Leitich et al, 1999: revisão 35 estudos que utilizaram comprimento colo predizer PPT. ● Sensibilidade de 68 a 100% ● Especificidade de 44 a 79% Hassan et al, 2000: 60% gestantes 2º trimestre com colo 1,5cm apresentaram PPT Freitas Jr, 2001: 23a semana colo 3,5cm (2,8 a 4,7)

36 Comprimento do colo uterino na 24ª semana e risco de Parto pré-termo (< 35sem)
JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med 1996;334: Copyright 1996 Massachusetts Medical Society The risk of preterm birth increased as the length of the cervix decreased.

37 Marcador ultra-sonográfico
PREDIÇÃO TPPT Marcador ultra-sonográfico

38 TPPT:DIAGNÓSTICO IG: 22 a 36 semanas
● Desconhecem a DUM ● Não realizam pré-natal ● Chegam trabalho de parto IG: 22 a 36 semanas Atividade uterina rítmica, dolorosa e perceptível à palpação (1a 2 contrações/20segundos/10minutos/1 hora) Toque vaginal: esvaecimento com ou sem dilatação 80% inibições TPPT são desnecessárias, porém a demora iniciar terapia tocolítica aumenta chance insucesso (fase ativa TP) Correa, 2004

39 TPPT:EXAMES PRÉVIOS À INIBIÇÃO Anatomia, vitalidade e maturidade fetal
Vitalidade fetal Hemograma Urina 1 e UCA ULTRA-SOM Integridade membranas cório-amnióticas Avaliação específica (doença materna) Anatomia, vitalidade e maturidade fetal

40 TPPT: ABORDAGEM 30% Medidas gerais: Internação
• Repouso • Hidratação (cuidado) • Controle doenças associadas • Evitar toques vaginais • Apoio psicoterápico Enfoque específico: drogas tocólise (parental) • Agonistas  adrenérgicos • Inibidores prostaglandinas • Sulfato magnésio • Bloqueadores canais cálcio • Atosiban • Nitroglicerina • Progesterona 30%

41 pinça aberta e 3000ml em 24 horas
TPPT: ABORDAGEM HIPERHIDRATAÇÃO Volume plasmático diminuído em 66% mulheres com trabalho parto pré-termo Goodlin et al., 1989 Soro fisiológico 1000ml pinça aberta e 3000ml em 24 horas

42 AGONISTAS  ADRENÉRGICOS (ETAMIMÉTICOS)
TPPT: INIBIÇÃO AGONISTAS  ADRENÉRGICOS (ETAMIMÉTICOS) Aumentam atividade adenilciclase reduzindo concentração de cálcio intracelular Terbutalina EV 1 ampola = 0,5mg de sulfato de terbutalina 2 a 5 amp/500ml SG5%/10gotas/min Salbutamol Custo: Ampola = R 2,15 R 21,50/d Efeitos colaterais: alterações metabólicas e cardiovasculares Edema pulmonar: hidratação+corticóide+ mimético

43 TPPT: INIBIÇÃO MANUTENÇÃO Terbutalina SC
Custo: Ampola = R 2,15 R 6,45/d MANUTENÇÃO Terbutalina SC 2 a 3h DU ausente 1amp (0,5mg), SC 8/8h /24h Contra-indicações: Gestantes diabéticas e cardiopatas, síndromes hemorrágicas e hiperfunção tireodeana

44 INIBIDORES DAS PROSTAGLANDINAS
TPPT: INIBIÇÃO INIBIDORES DAS PROSTAGLANDINAS Inibem a enzima ciclooxigenase Indometacina (Indocid®): supositório de 100mg 1 supositório via retal de 8/8 ou 12/12h por 72 h Custo: supositório = R 1,47 R 4,41/d IG: 24 a 33semanas Fechamento precoce ducto arterioso Controle US (oligohidrâmnio)

45 TPPT: INIBIÇÃO SULFATO DE MAGNÉSIO
• Supressão da transmissão nervosa fibra muscular uterina • Age como antagonista do cálcio na fibra miometrial DA: 5g EV lento DM: 2g EV 4 em 4h Gestante diabética e cardiopata Keirse, Cochrane Review,1995: comparação do sulfato de magnésio com placebo para inibir TPPT não mostrou diferença entre os grupos

46 TPPT: INIBIÇÃO BLOQUEADORES DOS CANAIS DE CÁLCIO
Inibem refluxo cálcio através membrana célula muscular, reduz cálcio intra-celular e diminui atividade miometrial Nifedipina (Adalat®): 20 a 30mg VO a cada 4h Nicardipina (Cardene®) Custo: cápsula = R 0,25 R 2,0/d Gestante diabética e cardiopata Papatsonis et al, 1997: trial multicêntrico randomizado e Oei et al, 1999: meta- análise Nifedipina foi mais efetiva que ritodrina para inibir TPPT e provocou menos efeitos colaterais King et al, 2002 (Cochrane Review): os bloqueadores de canais de cálcio deveriam ser a primeira escolha para inibir TPPT

47 TPPT: INIBIÇÃO ATOSIBAN (TRACTOCILE ®)
Inibidor seletivo, por competição, dos receptores ocitocina Eficácia semelhante a terbutalina, menos efeitos colaterais Prolonga gestação 5 a 7 dias Não apresentou eficácia antes 28ªs Alto custo Custo: Amp 0,9ml= R 147,00 7,5mg/ml Cabrol et al, 2001; The Worldwide Atosiban versus Beta Agonists Study Group, 2001; Aravinthan et al, 2003; Tsatsaris et al, 2004

48 TPPT: INIBIÇÃO Progesterona
Dodd et al., 2005 Metanálise de 1966 – 2005: 7 trabalhos randomizados Mulheres em TPPT que receberam progesterona apresentaram • Menores taxas PPT: RR 0,58 95% IC 0,48-0,70 • Menores taxas de RN BPN: RR 0,62 95% IC 0,49-0,78 Progesterona prolonga gravidez e pode reduzir mortalidade neonatal Não há evidências suficientes tipo, via e dose progesterona uso TPPT

49 ASSISTÊNCIA AO TPPT FETO < 750g individualizar
SITUAÇÕES ESPECIAIS: APRESENTAÇÃO PÉLVICA FETO < 750g individualizar FETO acima de 750g : cesariana

50 ASSISTÊNCIA AO TPPT SITUAÇÕES ESPECIAIS: GESTAÇÃO GEMELAR
Predomínio da indicação cesariana (incisão) Exceção: dilatação uterina avançada com 1º gemelar em apresentação cefálica

51 FETOS LIMITE DA VIABILIDADE
ASSISTÊNCIA AO TPPT SITUAÇÕES ESPECIAIS: FETOS LIMITE DA VIABILIDADE FETOS < 750g individualizar cada caso, se optar por investimento considerar risco gestação futura

52 TPPT:CONTROVÉRSIAS CORTICOINDUÇÃO/CORTICOPROTEÇÃO
Reduz incidência de SAR Reduz incidência de hemorragia cerebral Potencializa efeitos benéficos do surfactante exógeno Crowley, 2000-Cochrane Review IG: 24 a 34s Qual corticóide? betametasona Quando indicar e quantos ciclos realizar?

53 USO DE ANTIBIÓTICOS E TPPT
TPPT:CONTROVÉRSIAS USO DE ANTIBIÓTICOS E TPPT Winer, 2002: vantagens e desvantagens do uso de AB no TPPT com bolsa íntegra (revisão) Não se deve prescrever AB para TPPT com BI sem sinais de infecção Uso de AB mostra tendência a prolongar a gravidez e diminui taxa de infecção materna mas não mostra benefícios nos resultados perinatais

54 USO DE ANTIBIÓTICOS E TPPT
TPPT:CONTROVÉRSIAS USO DE ANTIBIÓTICOS E TPPT COCHRANE metanálise (2001): 8 trabalhos randomizados para avaliação de uso de antibióticos e placebo em gestantes com TPPT Não houve diferença entre os grupos no prolongamento da gravidez, na ocorrência PPT, SAR e sepsis neonatal. O grupo AB apresentou significativa redução do risco de infecção materna e enterocolite neonatal

55 USO DE ANTIBIÓTICOS E TPPT
TPPT:CONTROVÉRSIAS USO DE ANTIBIÓTICOS E TPPT Associação entre infecção e TPPT é clara, porém o uso de antibióticos para o tratamento do TPPT não é recomendado

56 Profilaxia antibiótica para SGB
TPPT:CONTROVÉRSIAS Profilaxia antibiótica para SGB CDC, 2002: parto antes de 37s administrar profilaxia para SGB, salvo paciente cultura negativa nas últimas 5 semanas King College, 2003: profilaxia para SGB pacientes com TPPT não deve ser realizada com conduta de rotina, pois profilaxia em gestantes para evitar a infecção em uma.

57 TPPT:FUTURO Prevenção infecções ascendentes TGI
Terapia profilática com heparina para trombofilias Refinamento das práticas de Reprodução Assistida Controle da resposta inflamatória (citocinas) As clinicians, our limited ability to stop preterm labor once it has started is equally as frustrating as our inadequate efforts to predict it. Strategies to prevent preterm delivery will most likely require interventions at an earlier stage in the process prior to initiation of the pathways leading to preterm birth. Management therapies to prevent ascending genital tract infections and to reduce excessive cytokine response are needed. Prophylactic heparin therapy should be evaluated for use in women with inherited or acquired thrombophilia who have recurrent premature deliveries due to placental abruptions or uteroplacental thrombosis. Artificial reproductive techniques have been largely responsible for the marked increase in multifetal gestations and must be refined to reduce the occurrence of twin and higher-order pregnancies. Additional research to better understand the mechanism of action for 17 alpha-hydroxyprogesterone caproate in preventing preterm labor may present opportunities to identify a broader application for its use among at-risk women. Source: Lockwood CJ. Predicting premature delivery–no easy task. N Engl J Med 2002;346:282-4.

58 TPPT:FUTURO Novas medicações: potentes, EC mínimos, prolonguem gravidez reduzindo morbidade/mortalidade perinatais, com custo acessível: Antagonistas dos receptores da PG F2 alfa Pesquisa dos 50% de TPPT de etiologia desconhecida ALTERAÇÕES GÊNICAS: genes que codificam enzima paraoxonase humana cuja variabilidade pode se associar com PPT (Chen et al, 2004)

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