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
Top Related