(ALGUNOS)
PROBLEMAS MEDICOS DURANTE LA GESTACION
MUNTHER A KAHAMASHTALUPUS RESEARCH UNITST. THOMAS’ HOSPITAL
LONDON, UK
GUILLERMO RUIZ-IRASTORZASERVICIO DE MEDICINA INTERNA
HOSPITAL DE CRUCES - UPV / EHUBARAKALDO, BIZKAIA
obstetricia en dos palabras
EMBARAZO NORMAL: 40 semanas
EMBARAZO A TERMINO: ≥ 37 semanas
PRIMER TRIMESTRE: hasta la 13 semana
SEGUNDO TRIMESTRE: 14-27 semanas
TERCER TRIMESTRE: desde la 28 semana
PUERPERIO: 8 semanas post parto
ABORTO: ≤ 10 semanas
MUERTE FETAL: > 10 semanas
ORGANOGENESIS: 5-9 semanas
cambios fisiológicos
Bajan:
• TA
• Hb
• Plaquetas
Suben:
• C3 y C4
• Filtrado glomerular (proteinuria)
toxemia (preeclapmsia-eclampsia)
2ª mitad del embarazo
Preeclampsia: HTA, proteinuria, edemas
• alteración analítica hepática
• trombopenia
• dolor abdominal
• cefalea
Eclampsia: + covulsiones
Pre-pregnancy counselling
Assess for risk factors
Stratify high / low risk
Give realistic, evidence based estimates for likely success and chance of problems
Discuss prematurity and handicap
Advise against pregnancy if appropriate
Make and agree prospective plan of care
What makes a pregnancy “high risk”?
Previous poor obstetric history
Renal involvement (Cr > 250umol/l)
Cardiac involvement
Pulmonary hypertension
Restrictive lung disease (FVC < 1 litre)
Active disease
Antiphospholipid syndrome
Extractable nuclear antigens (Ro, La)
IVF / multiple pregnancy
CASE 1
A 36 year-old female patient with SLEHistory of lupus nephritis 2000 (WHO class IV)Received CYCLO (NIH regimen) for 2 ½ yearsCurrent medications: PRED 7.5 mg/od, HCQ 200 mg/od, AZA 100
mg/od and lisinopril 2.5 mg/od
Pregnancy clinic assessment:
- SLE in remission
- Urine dipstick NAD - Anti-dsDNA +++- BP 130/85 . Normal renal function - Anti-Ro +- FBC normal - LA/aCL -ve- CRP <5.0 / ESR 30 - C3/C4 normal limits
No previous obstetric history – Considering pregnancy
Cyclophosphamide therapy in SLE
Ovarian failure
Permanent infertility: 30 - 50%Factors - age
- duration
Boumpas et al. Ann Intern Med 1993
Wang et al. Lupus 1995
Weekly low-dose (500mg) IV pulse therapy
Severe CTDLupus Nephritis Class III, IVNon-thrombotic CNS lupus
LACK OF OVARIAN TOXICITY
Ramos et al. Clin Exp Rheumatol 1996D’Cruz et al. Clin Exp Rheumatol 1997
Martin-Suarez et al. Ann Rheum Dis 1997
Cyclophosphamide therapy in SLE
•• Lockshin et Lockshin et al 1984al 1984
•• Mintz et Mintz et al 1986al 1986
•• Urowitz et Urowitz et al 1993al 1993
•• Wong et Wong et al 1991al 1991
•• PetriPetri et et al 1991al 1991
•• RuizRuiz--Irastorza etIrastorza et al 1996al 1996
NONO
YESYES
DOES PREGNANCY INCREASE SLE ACTIVITY?DOES PREGNANCY INCREASE SLE ACTIVITY?
Pregnancy and Lupus
50-60% of patients
Any time during pregnancy/postpartum
Most are mild
Good response to corticosteroids
Lupus flares
Ruiz-Irastorza et al. Scand J Rheumatol 1998
Renal involvement / hypertension
Increased risk of PET / IUGR / preterm delivery
Even quiescent lupus nephritis increases risk of fetal loss,
especially if hypertensive or proteinuric
Risk of deterioration is higher with higher serum creatinine
Chance of successful outcome is lower with higher serum
creatinine
Delay pregnancy for 6 months after renal flare
Degree of renal impairment
Germain & Nelson Piercy. Lupus 2006
MildCr<125
<1.4mg/dl
SevereCr > 250
>2.8 mg/dl
Problems 25% 50% 85%
IUGR 30% 60%
Preterm 55% 70%
Success 85-95% 60-90% ?20-30%
Moderate126-2491.4 - 2.8
--
--
Anti Ro / La antibodies
30% of women with SLE
Associated with photosensitivity, subacute LE, Sjögren’s
5% risk of neonatal cutaneous lupus
2% risk of congenital heart block
Offer fetal cardiology scan (18 and 32 weeks)
Neonatal cutaneous lupus
Manifests age 2-3 weeks
Geographical skin lesions
Face, scalp
After exposure to sun / UV light
• Disappears spontaneously within 6 months
• No scarring
Congenital Heart Block
Appears in utero (18-28 weeks)
Fetal bradycardia
50-60% of those who survive need pacemakers in early infancy (others in early teens)
Dexamethasone / Betamethasone / Salbutamol
Recurrence rate 20%
Pregnancy and Lupus
Women with lupus should not get pregnant
Most women with lupus can safelybecome pregnant and deliver a normal, healthy baby
Old medical Old medical textbookstextbooks
TodayToday
CASE 2
• A 24 year-old female patient with previous history of an intrauterine death at 6 months in 2005
• No clinical/laboratory evidence of lupus or other CTD
• LA persistently positive /aCL negative
• Physical examination unremarkable other than prominent livedo reticularis in lower limbs
• Planning for another pregnancy
What is your management plan for this patient??
Management of pregnancy in aPL-positive womenRecommendations
• No thrombosis / miscarriageNo treatment - Careful monitoringLow-dose aspirin (no evidence)
• Previous thrombosisHeparin + Low-dose aspirin
• Recurrent early miscarriageLow-dose aspirinHeparin + Low-dose aspirin
• Late fetal loss / severe pre-eclampsia / IUGRHeparin + Low-dose aspirin
• Try again with aspirin/heparin
• Add: ? low dose steroids
? IVIG
? hydroxychloroquine
? azathioprine
APS pregnancyWhat to do if aspirin/heparin fails?
Thromboprophylaxis is essentialThromboprophylaxis is essential……
Doctor, please
Doctor, pleasedondon’’t forget
t forget my mummy!
my mummy!
CASE 3
• A 24 year-old female patient with primary APS
• Left thigh DVT 10 years ago in the absence of other
hypercoagulable states
• On warfarin since then without recurrences
• Considering pregnancy for the first time
What is your advice?
How would you plan her pregnancy?
Maternal Increased bleeding risk
Fetal 1st trimester - teratogenic
(chondrodysplasia punctata)
2nd trimester - microcephaly
- optic atrophy
- mental retardation
3rd trimester - Intra cerebral bleeding
- Retroperitoneal bleeding
Risk of warfarin therapy in pregnancy
Thromboprophylaxis in pregnant women with previous thrombosis
Switch from warfarin to heparin when pregnancy is
confirmed
LMWH equally effective, safer and more convenient
ALWAYS add low-dose aspirin
Prevent osteoporosis (calcium + vitamin D)
What makes a pregnancy “high risk”?
Previous poor obstetric history
Renal involvement
Cardiac involvement
Pulmonary hypertension
Restrictive lung disease (FVC < 1 litre)
Active disease
Antiphospholipid syndrome
Extractable nuclear antigens (Ro, La)
IVF / multiple pregnancy
Manejo general
Coordinación médico - obstetra
Estabilidad previa al embarazo
• actividad LES
• trombosis
• HTA
Buscar signos de complicaciones:
• proteinuria
• HTA
• trombosis
• actividad inflamatoria
• doppler
Manejo general
Uterine artery Doppler analysis
Flow velocity waveformsFlow velocity waveforms(20(20--24 weeks)24 weeks)
Normal FVWNormal FVWlow RI, no low RI, no
notchnotch
Abnormal FVWAbnormal FVWhigh RI, early diastolichigh RI, early diastolic
notchnotch
Pregnancy Lactation
NSAID yes
(avoid after 32 weeks)
yes
Sulphasalazine yes yes
Antimalarials yes yes
Corticosteroids yes yes
Cyclosporin yes yes?
Azathioprine yes yes?
Mycophenolate no no
Methotrexate no no
Cyclophosphamide no no
Anti-TNF
Rituximab no no
Warfarin no
(with caution after first
trimester)
yes
Heparin yes yes
AAS (low dose) yes yes
Antirheumatic and antithrombotic drugs during pregnancy & lactation
Pregnancy Lactation
Methyldopa yes yes
Nifedipine yes yes
Hydralacin yes yes
Labetalol yes yes
Alpha-blockers yes yes
ACE-Inhbitors no yes
Antihypertensive drugs during pregnancy & lactation
Nelson-Piercy C. Handbook of obstetric medicine
Intervención terapeútica
LES: corticoides dosis bajas, HCQ, AZA
SAF: AAS +/- HBPM
Preeclampsia: AAS, Metil-dopa, Labetalol, finalizar
embarazo
BCC: betametasona / dexametasona
Cuidado con la osteoporosis !!!
Calcio + Vit D en pacientes con heparina
Limitar corticoides
En pacientes de alto riesgo (corticoides, baja DMO
previa…):
• Consejo sobre riesgo de lactancia
• Suplemento de calcio + Vit D en lactancia
Las reglas de oro
Estabilidad previa al embarazo
Control coordinado
No experimentar con los tratamientos
Prever complicaciones
Madre primero: en situaciones graves, fin de embarazo
Niño mejor a partir de la semana 28
y una buena Unidad Neonatal
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