(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

Lupus in pregnancy clinic Lupus in pregnancy clinic –– St ThomasSt Thomas’’ HospitalHospital

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

Neonatal lupus3 weeks

3 months

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??

Obstet Gynecol 2003; 101: 1333-44

Arthritis Rheum 2004; 50: 1028-39

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

85% success rate

• 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)

Heparin & WarfarinHeparin & Warfarin

Safe during breastfeeding

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

Doppler umbilical: insuficiencia placentaria

desde la 20 semana

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

Ecocardiograma fetal

y si necesita tratamiento….

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