Gilbert –Preeclampsia –3.9.10
Preecamplsia: Where we are
• Nationwide PE is a leading cause of maternal death and a major
contributor to maternal and perinatal morbidity
•In Minnesota PE is 2nd most common pregnancy complication
•Leading cause of premature delivery
•Women who develop preeclampsia and their IUGR babies
are at increased risk of cardiovascular disease later in life
•Formerly preeclamptic women have lower incidence of certain
types of cancer (e.g. breast)
•Offspring data remain unclear
•Idiopathic etiology - No effective treatment/prevention
strategies other than delivery.
Preeclampsia: risk factors
•Age > 35 yrs or < 20 yrs & obesity
•Parity
•Ethnicity (African-American, Native American)
•Family History or previous preeclamptic pregnancy
•Gestational diabetes, obesity, preexisting
hypertension/renal disease, BP, thrombophilia
•Higher order pregnancy (assisted repro preg)
•Autoimmune disorders (Antiphospholipid syndrome, lupus)
•Inter-pregnancy interval - age dept on mom
Mechanisms of placental insufficiency
poor placental invasion.
Cytotrophoblasts invade. Spiral arts converted from high to low
Resistance bed – doesn’t occur in pre-ecclampsia. Normal
=Makes it more like a vein so not responsive to vasoconstrictors.
Etiology
makes it look more like vein. If it doesn’t occur, then reduced bld
flow to fetus
Genetic, environ and immune components. The PLACENTA plays
a central roll! Elaborates a variety of factors  HTN, renal func,
seizures, headaches, and liver problems
can use doppler flow to assess. Y = velocity, X = time. Up =
normal forward flow during systole, below X = bad  reverse
flow. L = pre-eccampsia. R =normal.
Gilbert –Preeclampsia –3.9.10
Angiogenic factors: the link between placental
ischemia and hypertension during preeclampsia
as plasma vol expands and vessel converted to low R bed 
greater diastolic spread. So in late pregnancy, it has smooth high
flow low R setting.
endothelial dysfunc  affects renal func  HTN
bottom = pre-ecclampsia
can be done at 15 wks to ID high risk pts
ID markers:
COMT = discussed in neuro/psych
PAPP-A = preg assoc plasma proteins
Oxidative stress = trying to Tx with vitamins never has the
desired effect.
AT1-AA: Angiotensin Autoantibodies
-Some of these markers are also associated in mammary
development – may alter differentiation of epithelium and
reduced cancer rates seen in these women.
L = infarcts in preeclampsia. The fetus is undernourished.
Use animal studies: at the beginning of last trimester – place
clips on lower abdominal aorta & ovarian art  generate preecclampsic model.
-See changes in sFLT-1; VEGF dec.
Gilbert –Preeclampsia –3.9.10
-VEGF121 reduces high blood pressure associated with placental
ischemia – trying to ID factors that can reduce renal & vasc
changes. By adding VEGF to rats, we can bring BP back down to
normal by improving renal function – better GFR too.
-But, fetal weight in RUPP animals Tx with high dose VEGF
doesn’t return to normal. Makes us wonder what the appropriate
BP targets are – the High BP could be a compensation to get bld
to fetus. The placenta lacks the normal autoreg capacity like
other organs.
-sFlt-1 receptor decreased in RUPP rats by exogenous VEGF121
infusion
-ratios of hormones maybe the important factors, it may be
enough to keep bp low enough.
Could timing of ischemia be important?
The timing of reduced bld flow plays a role in if a woman has just
a growth restricted baby or a woman who has pre-ecclampsia
with growth restricted baby.
late preg grp gives you an inc in all the assoc factors
-early grp give you growth restriction—bp went up in this grp
but not as much as late group.
-Timing of Placental ischemia influences maternal sFlt-1
concentrations
Long term effects of Preeclampsia
•Moms
•Decreased cancer incidence
•Glucose intolerance (T2DM)
•Endothelial dysfunction
•Increased risk of CVD, hypertension, etc.
•Kids
•Increased risk of CVD, hypertension, etc.
•Altered incidence of cancer
His research:
Formerly RUPP rats show no evidence of glucose intolerance (dif
than European human studies)
-Formerly RUPP rats have endothelial dysfunction in renal
microvessels that is attenuated by the antioxidant Tempol
-bld vessels don’t relax as much in stim to Ach
-this dif may be mediated by oxidants – so admin
tempol
-Increased breast cancer susceptibility in IUGR (Intrauterine
growth rate) offspring
-small babies have much greater likelihood for
developing cancer.
Future Directions
•Does exercise training before/during pregnancy prevent
hypertension associated with placental ischemia
-from animal studies – mix results if it alters fetal
growth.
-if you already exercise – no need to stop. If you don’t,
no need to start.
Future treatment of preeclampsia
•Prophylatic
•Exercise
•Symptom suppression = delayed treatment? (concern)
•Early identification: Enhanced perinatal care
•Symptom Treatment (hydralazine, VEGF, TGF-β, 2-ME, antioxidants?, etc.)
•Safely lengthen gestation
•Enhance maternal/fetal outcomes
Considerations for Preeclamptic Patients
•Preeclampsia as an independent risk factor
•Lifestyle modifications
•Proactive health care
-This is his research model – clinical studies, animal models, and
in vitro studies to develop effective strategies for prevention/Tx
of precclampsia
Practice Questions:
1. Describe the pathologic changes in the spiral arteries of
pre-ecclamptic patients
2. List 4 risk factors for pre-ecclampsia
3. What effect does VEGF have in pre-ecclampsia?
4. Describe the relationship between pre-ecclampsia and
breast cancer.
Answers
1. Spiral artery converted from high to low Resistance bed
– doesn’t occur in pre-ecclampsia. Normal =Makes it
more like a vein so not responsive to vasoconstrictors
2. •Age > 35 yrs or < 20 yrs & obesity
•Parity
•Ethnicity (African-American, Native American)
•Family History or previous preeclamptic pregnancy
•Gestational diabetes, obesity, preexisting
hypertension/renal disease, BP, thrombophilia
•Higher order pregnancy (assisted repro preg)
•Autoimmune disorders (Antiphospholipid syndrome,
lupus)
•Inter-pregnancy interval - age dept on mom
3. educes high blood pressure associated with placental
ischemia, but the doesn’t improve birth weight
4. Mom: Some of these markers are also associated in
mammary development – may alter differentiation of
epithelium and reduced cancer rates seen in these
women.
Baby: Increased breast cancer susceptibility in IUGR
(Intrauterine growth rate) offspring
-small babies have much greater likelihood for
developing cancer.