Miocardiopatías fetales

Dra. Magdalena Honorato S

CERPO

Centro de Referencia Perinatal Oriente

Facultad de Medicina, Universidad de Chile

Miocardiopatías fetales (MC)

Enfermedad que afecta el músculo cardíaco que no está relacionada con malformaciones estructurales cardíacas

Afectación de uno o ambos ventrículos

Puede llevar a falla cardíaca

Generalmente sin causa aparente

Recurrencia

Generalidades

8-11% cardiopatías diagnosticadas in útero

3% cardiopatías en RN

1/3 mortalidad

Se presentan entre las 22-24 semanas

Clasificación

Mocardiopatía dilatada

Miocardiopatía hipertrófica

Otras:

Restrictiva

No compactada

Diagnóstico Ecográfico

Sospecha diagnóstica

Aumento global tamaño cardíaco

Dilatación de cavidades

Engrosamiento e hiperecogenicidad de paredes vetriculares

Signos de disfunción sistólica/ diastólica

Ecocardiograma:

Fundamental para el diagnóstico

Morfológico

Funcional

Ecocardio fetal

Morfología

Aumento global tamaño corazón

Aumento ICT MCD

Dilatación cavidades cardíacas

Medición de diámetros ventriculares al final de la sístole y diástole MCD

Medición de grosor pared ventricular al final de sístole y diástole MCH

Puede existir hiperecogenicidad de paredes ventriculares

Fibroelastosis endocárdica

Morfología

MCD

Disminución contractibilidad: Fracción acortamiento < 28%

Crecimiento ventricular > 97.5% EG

No compactada

Observación de trabeculaciones con penetrancia de vasos en el espesor de la pared

MCH

Grosor pared > 97,5% EG

Función

Disfunción sistólica VD o VI

Fracción de acortamiento < o = 28% ( <2DE)

Disfunción diastólica: al menos 2 de los siguientes

Relación E/A anormal en mitral o tricúspide

Aumento en el t de relajación isovolumétrico ventricular

Alteración de la onda a en VCI o Vena hepática ( >20cm/ seg)

Vena umbilical pulsátil

Hidrops fetal

Diagnosis and Prognosis of Fetal Cardiomyopathies Current Pharmaceutical Design, 2010, Vol. 16, No. 26 2931

merous prominent trabeculations with deep myocardial recesses [13-15].

In the HCM the diagnosis is made on the basis of an increased

parietal thickness above 97.5% of normal standards for gestational age [16,17].

A hemodynamic evaluation can be performed by Doppler mode; pulsed and Color Doppler examination should always be performed and pulsed Doppler wave forms are analyzed at the level

of the inferior vena cava, hepatic vein (Fig. 5), ductus venosus and umbilical artery, at the level of the atrioventricular (Fig. 6) and semilunar valves, at the level of the outflow tract of the ventricles

and at the level of the great vessels. Presence of valves regurgita-tion should be documented (Fig. 6). With the Doppler analysis we can measure the left ventricular

isovolumic relaxation time (IVRT).

Fig. (4). Isolated non-compaction of the left ventricle at 28 weeks in gesta-

tion: the fetal echocardiogram shows the persistence of marked ventricular

trabeculations and deep intertrabecular recesses.

Fig. (5). Doppler tracings observed in the diastolic function assessment: a

fetus with DCM at 26 weeks in gestation with an increased a-wave reversal

in the hepatic vein.

Systolic and diastolic fetal cardiac functions have become a part

of the routine evaluation of the fetal heart. It has been suggested, in

particular, that diastolic function parameters may provide key prog-

nostic information in several fetal conditions, including cardiomy-

opathies [18].

Fig. (6). Doppler tracings observed in the diastolic function assessment: a

fetus with INVM at 28 weeks in gestation. Fetal Doppler demonstrates

abnormal E/A ratio (E>A) and mitral valve regurgitation.

Left and right ventricular systolic function is evaluated by cal-

culating the shortening fraction (SF). Systolic dysfunction of the left

or right ventricle is diagnosed when the SF was 28% (< 2 standard deviations (SD) below the mean for previously published normal

data) [18]. Diastolic dysfunction is proposed [6] when at least two of the following parameters were

identified: abnormal E/A ratio

through mitral (Fig. 6) or tricuspid valve inflow (<2 SD below the

mean for gestational age based on the published data [19], increased

duration of IVRT (>2 SD above the mean for gestational age based

on the published data[19], increased a-wave reversal in the inferior

vena cava or hepatic vein (>20 cm/s) (Fig. 5) or a biphasic rather

than triphasic flow pattern, and the presence of umbilical venous

pulsations. In the absence of sinus rhythm, the presence or absence

of umbilical venous pulsations is the only Doppler parameter used

to evaluate diastolic function. Fetal hydrops

is diagnosed of a mod-

erate degree when three sites are identified (hydropericardium,

ascites, hydrothorax). Hydrops is mild when at least two sites of

fluid collections were identified and severe with associated skull

edema.

DILATED CARDIOMYOPATHY

Dilated cardiomyopathy is a very rare disease in fetuses. Only isolated case reports and small case series have been reported. The

published study suggests a very poor outcome for affected fetuses.

We define an adult patient affected by DCM when he has dila-tation of the cardiac chambers and systolic dysfunction, and also the fetuses with systolic univentricular or biventricular dysfunction as

affected by dilated cardiomyopathy, with or without chambers di-latations and without increased wall thickness.

Schmidt et al. [20] in 1986 established the diagnosis of DCM in 6 out of 625 fetuses studied by echocardiography. In all fetuses cardiac structural abnormalities were excluded. Abnormal findings

included reduced fractional shortening index in 5 patients, 3 were affected by atrioventricular valve regurgitation, 3 with abnormal chamber dimensions and 4 with non-immune hydrops. In 2 fetuses

with a positive family history of dialated cardiomyopathy, echocar-diographical abnormalities were absent on a first examination per-

formed during 20 weeks of gestation, but they were present at 30

weeks of gestation. This suggested that a normal fetal echocardio-gram in a midtrimester fetus does not always rule out the subse-quent development of dilated cardiomyopathy. About the natural

history, only 2 infants (33%) survived, 1 of whom required heart transplantation during infancy. Death from cardiac failure occurred in 1 fetus and 3 newborns.

Compromiso de la función

Sistólica:

MCD casi 100%

MCH 50%

Diastólica

MCD/ H 60%

Miocardiopatía Hipertrófica

Aumento de masa o grosor pared ventricular Causas

DM: hipertrofia septal principalmente Metabolismo anabólico de la hiperinsulinemia y acumulación de glucógeno

en el 3º trimestre

RCIU STFF Primarias: genes codifican proteinas contráctiles del sarcómero

B miosia y proteina C ligada a la miosina

Asociación a Sd. Noonan y mutaciones ADN mitocondrial Desconocida

Buen pronóstico: regresión completa en 6 meses sobre todo sin relación a otras anomalías cardíacas

2930 Current Pharmaceutical Design, 2010, Vol. 16, No. 26 Mongiovì et al.

vernix after the first trimester of pregnancy, has a weak electrical conductivity. Because the electrical activities of the heart cause

weak changes of the magnetic field, a non-invasive technique, the fetal magnetocardiogram, based on the measurement of the mag-

netic fields produced in association with cardiac electrical activity,

provides better signal quality than ECG because of more favorable transmission properties of magnetic signal. This technique has

higher resolutions in time domain than echocardiography. There are

many limitations due to significant costs, employment of trained personnel, requirement of a magnetically shielded room, and im-

mobility of the fetus during the exam. For these reasons, fetal mag-

netocardiography does not provide a real solution to fetal ECG analysis but it can be helpful in selected conditions. In fact it is the

best available method to diagnose LQTS, by acquiring an accurate

averaged signal of the PQRST Complex. In another recent study [4], magnetocardiography was used to better define fetal T-wave

characteristics including the QT interval in the normal fetus, and to characterize T-wave with the assessment of QT interval and T-wave alternans abnormalities in the fetus with arrhythmia.

For these reasons and with published studies we will describe

the fetal CM starting from their echocardiographic presentation:

dilated cardiomyopathy (DCM) with dilatation of either or both ventricles, and impaired ventricular function (Figs. 1-2), and hyper-

trophic cardiomyopathy (HCM) with different degrees of dispropor-

tionate hypertrophy of the myocardial walls (Fig. 3).

Fig. (1). Fetal echocardiogram demonstrating the 4-chamber view in a case

of DCM interesting only left ventricle.

Fig. (2). Fetal echocardiogram at 26 weeks in gestation showing the 4-

chamber view in a biventricular DCM.

Fig. (3). Fetal echocardiogram at 22 weeks in gestation showing a 4-

chamber view in a HCM.

FETAL SPECTRUM

The CM in the human fetus are a very rare pathology and the

studies about the prevalence, the pathogenic causes, the echocar-diographic and the hemodynamic aspects, and about the history of the disease before and after birth.

The frequency of CM in the fetal life is difficult to establish because the reports often included atherogenic cases with specific

conditions like twin-to-twin transfusion syndrome, cases of anemia or hypertrophic cardiomyopathy associated with maternal diabetes.

In a series of neonates and infants the CM occur in about 2-7%, but probably during the fetal life the prevalence is higher: CM ac-

count for 8% - 11% of the cardiovascular diagnoses detected in utero [5,6], 6.7% (53/847) in the Multicenter study of Italian Soci-ety of Pediatric Cardiology [7]. The high intrauterine loss, occur-

ring in one-third of the affected fetuses, likely accounts for these

differences.

In the era of fetal echocardiography, the referral for suspected CM included family

history of CM, bradycardia or other dysrhyth-

mia, maternal diabetes, cystic hygroma, pleural effusion or hydrops

fetalis, multiple malformations, suspected twin-twin transfusion

syndrome and dilated or thickened heart. Gestational age at presen-

tation was different with high range between 18 to 36, but usually

near 22 - 24 weeks, with no difference in the age at presentation

between HCM and DCM groups. CM may develop during fetal life and may be diagnosed by prenatal echocardiography even if a nor-

mal cardiac finding in a midtrimester fetus does not exclude a sub-sequent CM development. Fetal cardiomyopathies can be isolated or associated with other cardiac and non cardiac malformations,

such as congenital cardiopathy or hydrops [8].

INSTRUMENTAL DIAGNOSIS

Fetal echocardiography is the main diagnostic tool and it is useful for the therapeutic orientation and to determine the neonatal outcome. Fetal cardiomyopathies can be analyzed by studying atrial

and ventricular contraction using B and M-mode echocardiography. Left and right ventricular end-systolic

and end-diastolic diameters

and wall thickness are measured

from M-mode tracings or 2-

dimensional images as previously described [9,10]. Cardiothoracic ratio is measured from cross-sectional

images through the thorax.

The criteria for the diagnosis of DCM are reduced contractility (shortening fraction < 28%) and the ventricular enlargement above the 97.5% according to the normal standards for gestational age

[11,12] without thickening of the walls.

The term of the “noncompaction” of the left ventricular myo-

cardium (Fig. 4), is used in cases with DCM with evidence of nu-

Miocardiopatía Hipertrófica

Zielinski et al, entre Marzo 87 y Abril 1991, se revisaron 283 casos fetales con diagnóstico de MCH, principalmente septal EG 32 sem 92.3% asociados a DM > regresión espontánea hipertrofia y normalización post parto

Pedra et al, 1997, se revisaron 33 caso de MCH 7 DM 2 Sd. Noonan 2 alfa talasemia homocigoto 1 historia familiar de MCH 18 receptores de STFF 3 idiopáticos Tasa de mortalidad 51.7%

Miocardiopatía Dilatada

Dilatación cavidad ventricular + Disfunción sistólica Muy raro en fetos

Serie de casos publicados Alta mortalidad:

Disfunción diastólica y regurgitación val. A-V Hidrops 60%

Múltiples causas: 25% infecciosas: TORCH, coxsackie, adenovirus, parvovirus

B19, VIH, micobacterias, parásitos, etc Estudio serología materna Amniocentesis o Cordocentesis

OH Quimioterapia Autoinmune: Anti RO-LA Familares de penetrancia variable, AD o ligados a crom X.

2930 Current Pharmaceutical Design, 2010, Vol. 16, No. 26 Mongiovì et al.

vernix after the first trimester of pregnancy, has a weak electrical

conductivity. Because the electrical activities of the heart cause

weak changes of the magnetic field, a non-invasive technique, the fetal magnetocardiogram, based on the measurement of the mag-netic fields produced in association with cardiac electrical activity,

provides better signal quality than ECG because of more favorable transmission properties of magnetic signal. This technique has

higher resolutions in time domain than echocardiography. There are

many limitations due to significant costs, employment of trained personnel, requirement of a magnetically shielded room, and im-

mobility of the fetus during the exam. For these reasons, fetal mag-

netocardiography does not provide a real solution to fetal ECG analysis but it can be helpful in selected conditions. In fact it is the best available method to diagnose LQTS, by acquiring an accurate

averaged signal of the PQRST Complex. In another recent study [4], magnetocardiography was used to better define fetal T-wave characteristics including the QT interval in the normal fetus, and to

characterize T-wave with the assessment of QT interval and T-wave alternans abnormalities in the fetus with arrhythmia.

For these reasons and with published studies we will describe

the fetal CM starting from their echocardiographic presentation: dilated cardiomyopathy (DCM) with dilatation of either or both ventricles, and impaired ventricular function (Figs. 1-2), and hyper-

trophic cardiomyopathy (HCM) with different degrees of dispropor-

tionate hypertrophy of the myocardial walls (Fig. 3).

Fig. (1). Fetal echocardiogram demonstrating the 4-chamber view in a case

of DCM interesting only left ventricle.

Fig. (2). Fetal echocardiogram at 26 weeks in gestation showing the 4-

chamber view in a biventricular DCM.

Fig. (3). Fetal echocardiogram at 22 weeks in gestation showing a 4-

chamber view in a HCM.

FETAL SPECTRUM

The CM in the human fetus are a very rare pathology and the studies about the prevalence, the pathogenic causes, the echocar-

diographic and the hemodynamic aspects, and about the history of the disease before and after birth.

The frequency of CM in the fetal life is difficult to establish because the reports often included atherogenic cases with specific conditions like twin-to-twin transfusion syndrome, cases of anemia

or hypertrophic cardiomyopathy associated with maternal diabetes.

In a series of neonates and infants the CM occur in about 2-7%, but probably during the fetal life the prevalence is higher: CM ac-count for 8% - 11% of the cardiovascular diagnoses detected in

utero [5,6], 6.7% (53/847) in the Multicenter study of Italian Soci-ety of Pediatric Cardiology [7]. The high intrauterine loss, occur-ring in one-third of the affected fetuses, likely

accounts for these

differences.

In the era of fetal echocardiography, the referral for suspected

CM included family history of CM, bradycardia or other dysrhyth-

mia, maternal diabetes, cystic hygroma, pleural effusion or hydrops

fetalis, multiple malformations, suspected twin-twin transfusion

syndrome and dilated or thickened heart. Gestational age at presen-

tation was different with high range between 18 to 36, but usually

near 22 - 24 weeks, with no difference in the age at presentation

between HCM and DCM groups. CM may develop during fetal life and may be diagnosed by prenatal echocardiography even if a nor-

mal cardiac finding in a midtrimester fetus does not exclude a sub-

sequent CM development. Fetal cardiomyopathies can be isolated or associated with other cardiac and non cardiac malformations, such as congenital cardiopathy or hydrops [8].

INSTRUMENTAL DIAGNOSIS

Fetal echocardiography is the main diagnostic tool and it is

useful for the therapeutic orientation and to determine the neonatal outcome. Fetal cardiomyopathies can be analyzed by studying atrial and ventricular contraction using B and M-mode echocardiography.

Left and right ventricular end-systolic and end-diastolic diameters

and wall thickness are measured

from M-mode tracings or 2-

dimensional images as previously described [9,10]. Cardiothoracic ratio is measured from cross-sectional

images through the thorax.

The criteria for the diagnosis of DCM are reduced contractility

(shortening fraction < 28%) and the ventricular enlargement above the 97.5% according to the normal standards for gestational age

[11,12] without thickening of the walls.

The term of the “noncompaction” of the left ventricular myo-

cardium (Fig. 4), is used in cases with DCM with evidence of nu-

Pedra et al, 1990-1999, Canadá, se revisaron 22 casos

2 CMV

5 casos familiares

6 fibroelastosis endocárdica relacionados con anti RO/LA

9 idiopáticos

Todos con disfunción sistólica

> 50% disfunción diastólica y regurgitación valvular av

Alta mortalidad: 82.3%

Sivasankarnan et al, 1983-2003

50 casos

24 MCD biventricular

17 MCD derecha

9 MCD izquierda

2/3 hidrópicos en algún momento de la gestación

Alta tasa de muerte intrauterina o neonatal precoz

37 casos se logra identificar causa de MCD: genética, metabólica, infecciosa, anemia, etc.

Hidrops: factor mal pronóstico

80% mortalidad

No Compactada Asociado a MCD Baja frecuencia

Presencia de trabeculaciones ventriculares, que son marcadas,

con profundos surcos intratrabeculares y con irrigación vascular directa por las cavidades ventriculares

Se han descrito causas genéticas, metabólicas, asociado a cardiopatías, etc

Asociado a miocarditis, hidrops, disfunción diastólica/ sistólica, regurgitación valulvar av y presentación temprana Alta mortalidad

Recurrencia 20-55%

Miocardiopatia Restrictiva

Rara en la vida fetal

Fisiología ventricular restrictiva con un patrón de llenado ventricular reducido 2ª a rigidez miocardio

Aumento de presión con escaso aumento de volumen

Disfunción diastólica

Hipertrofia ventricular con crecimiento auricular bilateral

Insuficiencia valvular

Alta tasa mortalidad fetal

Tratamiento

Mala respuesta

Infecciones

IG

Corticoides

Interrupción del embarazo

Caso Clínico CERPO

G. C. 19 años Concepción Antecedente de MNN por MC

Rederivada a CERPO por CC Consejería genética para estudio de ambos progenitores

DG:

MC no compactada con bradicardia fetal: LCF 93 Polihidroamnios Alteración doppler fetal RCIU < p3

Progresivo compromiso de la función cardíaca y alteración doppler fetal

Conclusión

Enfermedades raras: 6-11% cardiopatías Se asocian a una amplia variedad de condiciones

intrauterinas o genéticas Ecocardio principal instrumento diagnóstico Mal pronóstico

Excepto asociado a DM

Diagnóstico incluye Ecocardio, Eco anatomía, laboratorio materno y fetal

Consejo prenatal dificil Recurrencia Pocas opciones terapéuticas

Gracias

Referencias

Cardiología fetal, Galindo Medicina fetal, Gratacos Diagnosis and Prognosis of Fetal Cardiomyopathies: A Review , Maurizio Mongiovi*, Vlasta Fesslova#,

Giovanni Fazio, Giuseppe Barbaro# and Salvatore Pipitone, Current Pharmaceutical Design, 2010, 16, 2929-2934

Fetal Cardiomyopathies, Pathogenic Mechanisms, Hemodynamic Findings, and Clinical Outcome , Simone R.F.F. Pedra, MD; Jeffrey F. Smallhorn, MBBS; Greg Ryan, MB; David Chitayat, MD; Glenn P. Taylor, MD; Rubina Khan, MD; Mohamed Abdolell, MSc; Lisa K. Hornberger, MD, Circulation. 2002; 106:585-591

Bell DS. Heart failure: the frequent, forgotten, and often fatal com- plication of diabetes. Diabetes Care 2003; 26: 2433-41.

Sardesai MG, Gray AA, McGrath MM, Ford SE. Fatal hypertro- phic cardiomyopathy in the fetus of a woman with diabetes. Obstet Gynecol 2001; 98: 925-7.

Litvinova MF. Pathogenesis of hypertrophic cardiomyopathy in a fetus during insulin-dependent diabetes in a mother. Biull Eksp Biol Med 1996; 121: 698-701.

Rizzo G, Arduini D, Romanini C. Accelerated cardiac growth and abnormal cardiac flow in fetuses of type I diabetic mothers. Obstet Gynecol 1992; 80: 369-76.

Sheehan PQ, Rowland TW, Shah BL, McGravey VJ, Reiter EO. Maternal diabetic control and hypertrophic cardiomyopathy in in- fants of diabetic mothers. Clin Pediatr 1986; 25: 266-71.

Zielinsky P. Role of prenatal echocardiography in the study of hypertrophic cardiomyopathy in the fetus. Echocardiography 1991; 8: 661-8.

Vaillant MC, Chantepie A, Casasoprana A, et al. Transient hyper- trophic cardiomyopathy in neonates after acute fetal distress. Pediatr Cardiol 1997; 18: 52-6.

Introducción

Embarazos múltiples han aumentado en países desarrollados.

En EEUU 2014 --> 33.9 por 1000 RN.

La tasa más alta.

Embarazos múltiples tienen alta morbi mortalidad materna, perinatal e infantil.

Alto costo para la salud

La alta moribimortalidad perinatal esta dada por el alto riesgo de parto prematuro.

Embarazos < 32 semanas , < 37 semanas Son 8 a 9 veces

mayores que en embarazos únicos.

Introducción Muchas intervenciones han sido propuestas para evitar PP

gemelar

Reposo en cama, tocolíticos profilácticos, progesterona vaginal, caproato progesterona, cerclaje y pesarios.

No han logrado reducir incidencia PP.

Cuello corto es uno de los principales factores riesgo para PP

< 25 mm

Predictor más potente en embarazos únicos/ múltiples.

Uso de progesterona vaginal en embarazos múltiples ha sido menos estudiado.

Método

Base de datos y búsqueda:

MEDLINE, EMBASE, POPLINE, CINAHL and LILACS, the Cochrane Central Register of Controlled Trials y Research Registers de estudios emergentes.

Palabras claves: progesterona, parto prematuro, estudio controlado randomizado y embarazo gemelar.

Método

Selección estudio:

Estudios randomizados controlados en los que se randomizara mujeres con embarazo múltiple con Cx <25 mm durante segundo trimestre, a recibir progesterona vaginal o placebo/ sin tratamiento para la prevención del PP y /o resultados adversos perinatales.

Seleccionó aquellos cuyo objetivo principal fuera disminuir la tasa de PP por cervix corto.

Método

Criterios exclusión:

Estudios cuasirandomizados, a los trabajo de parto prematuro y aquellos frenados con tocólisis, RPO, hemorragia durante segundo trimestre, uso de progesterona en 1er trimestre para prevenir pérdidas.

Aquellos que no contaran con descripción metodología y resultados.

Los estudios seleccionados eran revisados por 2 autores para confirmar inclusión.

Método

Recolección datos:

Autores de estudios seleccionados aportaron información sin identificación pacientes, características y resultados.

Base de datos exclusiva para el estudio.

Consentimientos obtenido en el estudio original.

Método

Outcome primario: Parto prematuro < 33 semanas

Outcome secundario:

PP < 37, < 36, < 35, < 34, < 32, < 30 y < 28 semanas, SDR, enterocolitis necrotizante, hemorragia interventricular, sepsis neonatal, retinopatía, muerte fetal, neonatal, perinatal.

Mortalidad y morbilidad: peso nacer < 2500 grs y < 1500grs, ingreso a UCI, ventilación mecánica, outcomes neurológicos a largo plazo

Método

Análisis

Mujeres y fetos gemelares randomizados, y realizaron análisis con intención de tratar.

Para resultados adversos se estimó RR.

Para evitar conclusión incorrecta, sin relación dependiente se utilizó modelo lineal

El NNT para beneficio se calculó con CI 95%, para resultados con significancia estadística.

El estudio de subgrupos (Cx, dosis, historia obstétrica) se realizo con P > o = 0.05, para indicar que efecto tratamiento no difería significativamente en subgrupos

Resultados

5 estudios eran doble ciego, con placebo. El estudio restante

progesterona vs no tratamiento.

2 estudios dirigidos al efecto

de progesterona en cx corto.

Estudio de gemelar con Cx 20 – 25 en tto con progesterona aporto 224 madres y 448 fetos. Otros estudios aportaron 79

madres y 158 fetos.

Resultados

Resultados

Progesterona vaginal y parto pretérmino: PP < 33 semanas

31.4% vs 43.1%, RR 0,69 (95% CI, 0.51 – 0.93, P 0.01)

Outcome secundario:

< 35 semanas (RR, 0.83 (95% CI, 0.69 – 0.99) <34 semanas (RR, 0.71 (95% CI, 0.56–0.91) <32 semanas (RR, 0.51 (95% CI, 0.34–0.77) < 30 semanas (RR, 0.47 (95% CI, 0.25–0.86)

Sin diferencias significativas en PP < 37 semanas, < 36 semanas y < 28

semanas.

NNT para prevenir un PP < 30 y < 35 semanas varía entre 6 y 12.

Resultados

Resultados

Efecto de progesterona vaginal y resultados adversos neonatales.

Resultados

Resultados

Progesterona vaginal resultados neurológicos a largo plazo

2 estudios investigaron efecto exposición prenatal a progesterona vaginal y efectos neurológicos.

Estudio excluido no había diferencia significativa con retraso

desarrollo al estar expuesto a la progesterona, en un seguimiento a 55 meses.

Estudio incluido: Estudio desarrollo en expuestos progesterona 225 vs placebo 212 en un seguimiento a 57 meses.

• A través cuestionarios (ASQ)

• Mayor puntaje en grupo tratado con progesterona

• No habían diferencias significativas para estudiar riesgo bajo puntaje ASQ.

Discusión

Principal hallazgo Meta análisis demuestra que

la administración de progesterona vaginal a mujeres asintomáticas con embarazo gemelar durante segundo trimestre con cervix corto reduce:

Riesgo parto prematuro < 33 semanas 31%

Riesgo de muerte neonatal 47%

Discusión

Outcome secundario Pacientes que recibieron progesterona tienen disminución significativa en PP < 35, < 34, < 32, y < 30 semanas, muerte perinatal, y morbi mortalidad, SDR, peso al nacer < 1500 grs y uso ventilación mecánica.

Sin diferencias en desarrollo neurológico al seguimiento a las 4 – 5 años.

Discusión

Análisis de subgrupos

Pacientes con CX entre 10 y 20 mm o aquellos en tto progesterona 400mg/ día, parecen tener mayor reducción en el riesgo de tener parto prematuro < 33 semanas y muerte neonatal.

Sin embargo el análisis de categorías como CX < 10mm, progesterona en dosis 100 – 200 mg e historia de PP espontáneo están realizadas en base a grupo menor de pacientes.

Discusión

Falta de estudio a largo plazo de efecto de progesterona en desarrollo neurológico.

761 niños que participaron en estudio placebo con progesterona para prevenir PP, fueron evaluados a los 56 meses.

Sin diferencias significativas en el riesgo de retraso desarrollo

En estos estudios la progesterona no influyó en edad gestacional al parto.

Efecto neuroprotector de la progesterona.

Discusión

Falta estudio a largo plazo sobre resultados adversos de salud en gemelos expuestos a progesterona vaginal durante embarazo McNamara et al sin diferencias significativas entre

gemelos expuestos a progesterona vaginal vs placebo, con respecto a muerte, malformaciones congénitas, crecimiento, uso servicios salud y status global de salud a 3 – 6 años de edad.

Vedel etal. Tasas de diagnóstico relacionado a 10 órganos, sistema de admisión a hospital y estadía hospitalaria sin diferencias significativas hasta los 8 años de edad.

Discusión

Falta de efectos adversos maternos Serra et al:

Placebo vs progesterona 200 y 400 mg Efectos dosis dependientes y no significativos CIE

• 0% placebo • 1% 200 mg progesterona • 5% 400 mg progesterona.

El-Refaie et al.

Sin diferencias significativas en la tasa e CIE usando 400 mg (1% vs 0%) Tasas prurito y descarga vaginal, cefalea, rash y síntomas

gastrointestinales sin diferencias significativas. Régimen 400 mg/ día no esta asociado con efectos maternos adversos vs

200 mg o placebo.

Discusión

Limitaciones Solo 2 estudios fueron específicos en estudiar progesterona vaginal en

embarazos gemelares con cervix corto. 74% de la muestra de este meta análisis proviene de un solo estudio.

Incluye Cx 20 – 25 mm y no incluye grupo placebo control Obtuvieron resultados similares al excluir este estudio.

Reducción significativa del 39% en el riesgo de mortalidad y morbilidad neonatal fue obtenida sin incluir el estudio El-Refaie et al. No recolectó información sobre morbilidad neonatal: ECN, HIV, sepsis

neonatal, retinopatía.

Análisis de subgrupos incluyen un número pequeño de pacientes, lo que

limita el poder estadístico.

Conclusiones

Progesterona vaginal reduce riesgo parto pre término, morbilidad y mortalidad en pacientes con embarazo gemelar y un cervix corto.

Sin provocar efectos deletéreos en desarrollo neurológico en niñez.

Rol del cerclaje y pesario