Title: PEARLS FROM PREGNANCY
1PEARLS FROM PREGNANCY
- April 2002
- Karen M. Chacko, MD
2The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
3Gestational Diabetes Mellitus
- Formerly, every woman had 50 g OGTT done at 24-28
weeks - New (January 1999) ADA criteria exempt women lt25
years old, BMI lt27, no FHx, not Hispanic /Native
American /Asian /African American /Pacific
Islander - GDM complicates 4 of pregnancies
4Follow-up of GDM
- Greenberg (1995) 94 women with GDM given 75 g
OGTT at 6 weeks post-partum, 34 with abnl. test - 18 classified as IGT
- 16 classified as Diabetic
- IGT patients become diabetic at a rate of 1-5
per year
5Follow-up of GDM
- Greenberg, contd
- Three predictive variables
- insulin requirements
- poor glycemic control (2 hr pp gt150)
- 50g OGTT value (gt200)
- If insulin requirements were gt100 units/day, 100
of these women had an abnl. 6 week postpartum OGTT
6Follow-up of GDM
- Damm (1995) 91 women with diet-treated GDM given
75 gm OGTT at 8 weeks post-partum, 29.7 with
abnormal test - 16.5 classified as diabetic
- 13.2 with IGT
7Follow-up of GDM
- Kjos (1995) 675 Latino women with
diet-controlled GDM screened pp with 75 gm OGTT
and then followed at 5 years, overall 47
incidence of diabetes at 5 years - Initial OGTT diabetic at 5 years
- IGT 80
- normal 12
8Glycemic Control and Malformations
- Lucas (1989)correlated A1C at lt16 weeks gestation
to rate of malformations - HgbA1C none major minor
- gt10 64.7 11.8 23.5
- 8.0-9.9 87.1 4.8 8.1
- lt7.9 95.2 1.6 3.2
9Recommendations for the PCP
- ADA position if glucose levels are normal
postpartum after GDM, reassessment should be done
at a minimum every 3 years. Women with IGT/IFG
should have more frequent screening - Fasting glucose is acceptable as screening method
(do not have to employ an OGTT)
10The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
11Preeclampsia and Pregnancy
- Preeclampsia risk factors include
- Hypertension Extremes of Age
- Primigravid state Family History
- Obesity Renal Disease
- Diabetes mellitus Smoking (?)
- Hypercoagulable state Interbirth Interval
12Preeclampsia and Hypercoagulable States
- Several studies have looked at the incidence of
Factor V Leiden among women with preeclampsia
(Kupferminc, Dekkar, Lindoff, Dizon-Townson) - Studies done that include a full
hypercoagulable workup (Kupferminc, Dekkar)
13Preeclampsia and Factor V Leiden
of Patients
Lindoff
Dizon-Townson
14Preeclampsia and Hypercoagulable States
Dekkar
15Complicated Pregnancies and Hypercoagulable States
Kupferminc 1999
16Factor V and fetal loss
of patients
17Fetal Loss and Hypercoagulable States
of patients
Martinelli 2000
18Hypercoagulability and Recurrent Fetal Loss
- Foka 2000
- 80 Greek women with 2 or more losses and 100
controls - Greek population prevalence of Factor V 4.3 and
PT2.8
19Hypercoagulability and Recurrent Fetal Loss
- Foka contd
- 1st trimester 2nd trimester
- Factor V 14.7 31.5
- PT 8.1 10.5
20Thrombophilic Women and pregnancy
- Preston (1996) 571 women with known
thrombophilias followed during a collective 1524
pregnancies compared with 395 controls having
1019 pregnancies - Stillbirth OR 3.6 (1.4-9.4)
- Miscarriage OR 1.27 (0.94-1.71)
- Combined defects overall OR 14.3 (2.4-86)
21Recommendations for the PCP
- Perform a directed hypercoagulable workup in
women with a history of severe/early-onset/recurre
nt preeclampsia, stillbirths, fetal loss,
abruption, IUGR - With regards to miscarriage/stillbirth, primary
considerations should be lupus anticoagulant, PT,
and Factor V
22The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
23Hypertensive disorders of pregnancy
- Four basic subdivisions of hypertensive disorders
during pregnancy - Chronic hypertension
- Chronic with superimposed preeclampsia
- Preeclampsia or eclampsia
- Transient (gestational) hypertension/ PIH
-
-
24(Mis)classification schemes
- Fisher (1981) 176 pregnancies complicated by a
hypertensive disorder (almost all were labeled as
preeclamptic by chart review), all with renal
biopsy done postpartum - 54 with biopsy compatible with preeclampsia
alone - 25 primips incorrectly diagnosed
- 65 multips incorrectly diagnosed
25(Mis)classification schemes
- Reiter (1994) 186 women with HTN in pregnancy
BP, U/A, lytes, renal imaging, microscopy - 8 of preeclamptics found to have underlying
renal disorder (essential HTN, sponge kidney,
reflux nephropathy) - 16 of gestational HTN with underlying disorder
(essential HTN,sponge kidney, thin basement
membrane disease)
26Normalization of Blood Pressure
- Ferrazzani (1994)
- 159 women with gestational HTN
- mean of 6 days pp to normalization
- (DBP lt80 for 3 consecutive days)
- 110 women with preeclampsia
- mean of 16 days pp to normalization
- If gt50 days pp with elevated BP, reclassify as
chronic HTN
27Progression to Chronic Hypertension
- Adams (1961) avg 20 years of follow-up
- systolic gt140 diastolic gt90
- severe preecl. 43 40
- mild/PIH 58 60
- normotensive 26 21
- nulliparous 41 35
28Progression to Chronic Hypertension
of patients
29Predicting Ischemic Heart Disease
- Hannaford (1997) 214,356 woman-years of follow-up
- RR for preeclamptics vs. normotensives
- HTN 2.35 (CI 2.08-2.65)
- Acute mi 2.24 (CI 1.42-3.53)
- Chronic isch. 1.74 (CI 1.06-2.86)
- Heart Dz.
- Angina 1.53 (CI 1.09-2.15)
30Prediciting Ischemic Heart Disease
- Mann (1996) 77 women under the age of 45 with
acute mi and history of preeclampsia, 207
controls - preecl. plus RR p-value
- none 3.0 lt0.01
- cigarettes 3.8 lt0.01
- HTN 2.8 lt0.02
- OCPs 2.8 lt0.02
- all 2.8 lt0.05
31Recommendations for the PCP
- Women with a hypertensive disorder first
recognized during pregnancy should normalize BP
by 2 months maximum - Risk of progression to chronic HTN much higher in
women with gestational HTN/ PIH - Normotensive pregnancies predict decreased future
risk of hypertension - Hypertensive disorders may predict future risk of
ischemic heart disease
32The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
33DVT or PE during pregnancy or on OCPs
- PE is one of the leading causes of maternal
mortality - Pregnancy by itself will increase the levels of
coagulation factors I, VII, VIII, X and will
decrease the level of total Prot. S - 40 of postpartum DVTs present after discharge
from the hospital
34Factor V and VTE
- Faioni (1996) a series of 493 patients with
arterial or venous clot, 15 found to possess
Factor V Leiden (controls 2) - Among the female patients with Factor V, the
inciting event was felt to be pregnancy,
postpartum state, or OCP use in 67
35Factor V and VTE
- Hellgren (1995) women with DVT or PE during
pregnancy (n34), OCP use (n28), and controls
(n75) - 20/34 (59) of pregnant women with h/o
thrombosis with Factor V Leiden - 9/28 (32) of women on OCPs with thrombosis with
Factor V Leiden - 10 of controls with Factor V Leiden
36Pregnancy-related VTE
- Grandone (1998)
- 42 patients with DVT in pregnancy vs. 213
controls - coexistence ofgt1 mutation in 21.4
of patients
37Pregnancy-related VTE
- Gerhardt 2000
- 119 women with VTE during pregnancy or
puerperium, 223 controls
38OCPs and DVT
- Martinelli (1998) 80 patients with DVT (61 on
OCPs) vs. 120 controls (32 on OCPs) - DVT no DVT
- Factor V 19 3
- Prothrombin 18 3
- Prot C/S/ATIII/APLA 16 3
39Factor V and VTE
- Vandenbroucke (1994) 155 women with DVT and 169
controls without DVT - 35/155 (23) of women with DVT have Factor V
Leiden mutation vs. 6/169 (3.5) of controls - 109/155 (70) women on OCPs or with usage within
the 6 months prior to DVT - RR thrombosis from OCPs 3.8 (2.4-6.0)
- RR thrombosis with Factor V 7.9 (3.2-19.4)
- RR for OCPs plus Factor V 34.7 (7.8-154)
-
40DVT and Factor V
41Screening and OCPs?
- Vandenbroucke (1996) to prevent one death from
PE, 20,000 women with Factor V mutation would
have to be denied OCPs for one year and 400,000
women would have to be screened to find them - Middledorp (1998) in order to prevent 3 VTEs,
you would have to withhold 1000 carriers from OCPs
42Prophylaxis and Pregnancy?
- Middledorp (1998) if we were to use prophlyactic
heparin for Factor V carriers in pregnancy, 980
of 1000 women would be treated unnecessarily in
attempts to prevent a VTE
43Recommendations for the PCP
- Women with a DVT or PE during either pregnancy or
while on OCPs deserve a hypercoagulable work-up - Prophylaxis during pregnancy is not feasible
- Mass screening prior to prescribing OCPs has not
proven feasible - Women with a known disorder should never receive
combined OCPs
44The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
45Postpartum Thyroiditis
- Complicates 4-7 of pregnancies
- Incidence among Type 1 diabetics 22.5
- Biopsy shows lymphocytic infiltration
- Closely associated with presence of
anti-microsomal (anti-peroxidase) antibodies
46Postpartum thyroiditis - three phases
- Thyrotoxic phase (1-3 months) mild symptoms or
asymptomatic, decreased RAIU - Hypothyroid phase (4-8 months) clinically
hypothyroid or psychiatric symptoms - Euthyroid phase (within one year) significant
proportion go on to develop permanent
hypothyroidism
47Who is at risk for PPT?
- Mestman (1999), Gerstein (1993)
- previous pregnancy with PPT
- presence of antimicrosomal Ab
- FHx of thyroid disease
- TSH gt2 at 12 weeks gestation
- prior autoimmune disease, especially Type 1 DM
- HLA haplotypes assoc. with Hashimotos
48Postpartum Thyroiditis
- Anitmicrosomal antibodies are the most closely
correlated with the development of PPT - 10 of pregnant women overall will have positive
titers and of those with positive titers, 50 may
develop PPT - Positive titer yields OR of developing PPT 86.6
(45.9-163.2)
49Thyroiditis and Depression
- Harris (1992)
- 145 women , thyroid anitbody positive - 43
with postpartum mental illness - 229 women, thyroid antibody negative - 28
with postpartum mental illness - plt0.005
50Thyroiditis and Depression
- Pop (1993)
- 9/27 microsomal antibody positive women with
depression (33) - 52/266 microsomal antibody negative women with
depression (19.5) - RR for depression in antibody positive 1.73
- (CI 0.92-3.28)
51Incidence of Ongoing Hypothyroidism
of patients
52Treatment- PPT
- Hyperthyroid phase - nothing or beta-blockers
- Hypothyroid phase - often requires treatment with
L-thyroxine, wean after 6 months therapy and
recheck TSH
53Recommendations for the PCP
- TSH at one year postpartum in women with PPT or
history of pp depression - Yearly screening with TSH in women with prior
history of PPT as approximately 5 per year will
become hypothyroid - Screening prior to next pregnancy in women with a
history of PPT or Type I DM
54The Obstetric Interview
- Did you have diabetes during pregnancy?
- Did you have preeclampsia or complications during
pregnancy? - Did you have blood pressure problems during
pregnancy? - Did you have a clot during pregnancy or with OCP
use? - Did you have thyroid problems after pregnancy?
- Was your baby small at birth?
55Selected Etiologies of Low Birth Weight
- HTN
- Smoking
- Alcohol
- Cocaine/crack abuse
- Physical/mental abuse
56Mechanisms of Low Birth Weight
- Direct abruptio placentae, fetal fractures,
uterine rupture, liver/spleen rupture, pelvic
fractures, antepartum hemorrhage, premature
contractions, PROM, infection, exacerbation of
chronic conditions - Indirect decreased access to prenatal care,
increased stress, behavioral risks (smoking,
alcohol, drugs), inadequate nutrition
57HTN and Birth Weight
- Surian (1984) normotensive IUGR 2.3 and
hypertensive IUGR 15.6 - Bellomo (1999) neonatal weight in normotensive
pregnancies 3336 gm vs. an average weight of 2911
gm in hypertensives (plt0.001)
58Smoking and Birth Weight
- Overall, 26 of reproductive age women are
smokers and 31 of women between the ages of 8-34
years smoke at least 1 ppd (Fried, 1993) - Smoking accounts for 20-30 of low birth weight
babies and 10 of infant mortality - Babies are 150-250 gm (Fried, 1993) to 458 gm
(Bernstein, 1997) lighter on average vs.
nonsmokers
59Alcohol and Low Birth Weight
- Little (1980) women who were abstinent but
formerly alcoholic had birthweights 258 gm less
on average, current alcoholics were average 493
gm lighter - Passaro (1996) 10,539 women drinking 1-2
drinks/day with at least one binge or 3
drinks/day had a mean birthweight 150 gm less
60Cocaine and fetal outcome
- Associated with preterm labor, spontaneous
abortion, IUGR, limb reduction defects - Among women aged 18-25, estimated 4.8 have used
in the last year and 1.6 within the last month - Among women 26-34, 4.5 have used within the past
year and 1.1 within the last month (Richardson,
1993)
61Cocaine and Fetal Outcomes
Preterm
IUGR
LBW
Controls
of patients
Sprauve
Bateman
Calhoun
Cherukuri
62Frequency of Abuse
- Eisenstat (1999)
- 1/4 women are abused at some point during their
lives - 1/7 women have been abused within the past year
- 1/6 women are abused during pregnancy
63Picking up on Abuse
- Suspect if failure or delay in obtaining prenatal
care - Linked to complications in pregnancy
- miscarriage
- abruption
- PROM
- antepartum hemorrhage
- low birth weight
64Estimates of Abuse During Pregnancy
of patients
65Meta-Analysis of Abuse During Pregnancy
- Gazmararian (1996) meta-analysis of 13 studies
of prevalence of abuse during pregnancy (11/13
involved physical abuse only) - Estimated abuse in 3.9-8.3
- Studies asking gt1 time per patient or in the
third trimester range 7.4-20.1
66(Under)estimates of Abuse During Pregnancy
- McFarlane (1991)
- 8 of women reported abuse on a standard intake
form - 29 reported abuse when asked directly by a
physician
67Abuse and Low Birth Weight
- Bullock (1989) compared public and private
hospital settings along with abused and
non-abused women - battered controls p-value
- low b.w. 12.5 6.6 lt0.02
- private/lbw 17.5 4.2 lt0.001
- public/lbw 10.0 9.6 NS
68Recommendations for the PCP
- Recognize hidden underlying factors that can
predispose to low birth weight - Ask directed questions about abuse in addition to
already asked questions about smoking/alcohol/drug
s - Ask more than once
69Summary of Recommendations for the PCP
- Women with GDM should have screening for diabetes
and should be followed with yearly screening
thereafter - optimization of glucose control
prior to conception is crucial - Women with a hypertensive disorder are at
increased risk for chronic hypertension,
recurrent preeclampsia, and increased future
risk of ischemic heart disease
70Summary of Recommendations for the PCP
- Women with severe/early-onset preeclampsia, IUGR,
stillbirth or recurrent miscarriages should have
a hypercoagulable workup - Women with a DVT or PE during pregnancy or while
on OCPs need a hypercoagulable workup mass
screening prior to prescribing or conceiving not
indicated
71Summary of Recommendations for the PCP
- Women with a history of postpartum thyroiditis
are at high risk of becoming permanently
hypothyroid and need yearly TSH screening - Women with low birth weight babies could have a
number of different contributing factors,
including (but not limited to) tobacco, alcohol,
cocaine, and abuse
72(No Transcript)
73Case Presentation
- 16 y.o. G1P0 presented at 35 weeks gestation with
RUQ pain, BP 186/110, elevated transaminases,
platelet count of 114K, and urine dip 3 for
protein - She was hospitalized for preeclampsia and had a
normal delivery - Prior to discharge, she is started on a combined
OCP
74Case contd
- 2 months later, she returns with a DVT and
hepatic vein thrombosis - Workup included Prot C/S levels, Factor V Leiden
- all unrevealing - Past records from her pregnancy include a
prolonged PTT of 40.2 seconds (control 23.4-33.8
seconds)
75Case contd
- 11 dilutiion and RVVT both prolonged
- PTT corrected with phospholipid neutralization
test - Diagnosis antiphospholipid antibody syndrome
secondary to lupus anticoagulant - What would you have done if she had come to see
you post-partum prior to the use of combined OCPs
76Cost savings analysis
- Gregory (1993) assumed incidence of DM among GDM
pregnancies at 5 years 30-50 and a rate of
conversion to DM per year of 6.7 - Using dietary/exercise strategies, even if only
10 of cases were delayed for 10 years, 71
million 1990 dollars would be saved by the tenth
year
77(Mis)classification schemes
- Ihle (1987) 84 pts. with early-onset
preeclampsia 24 hr urine, U/A, lytes, biopsy (if
rbcs), IVP - 67 of primips had underlying renal
abnormalities - 63 of multips had underlying renal abnormalities
78Predicting Ischemic Heart Disease
- Jonsdottir (1995) follow-up of 7543 hypertensive
pregnancies for ischemic heart disease - Hypertensives vs. normals RR 1.47 (1.05-2.02)
- Eclamptics vs. normals RR 2.61 (1.11-6.12)
- Preeclamptics vs. normals RR 1.90 (1.02-3.52)
79Recurrent DVT
- DeStefano (1999) - general population
- RR first DVT (heterozygous Factor V) 7
- RR first DVT (homozygous Factor V) 80
- RR first DVT (heterozygous PT) 2.7-3.8
- RR recurrent DVT (hetero. Factor V) 1.1
- RR recurrent DVT (hetero. V/PT) 2.6
80Drugs and Abortion
- Ness (1999) 400 women with spontaneous abortion
vs. 570 women with intact pregnancy at 22 weeks.
Hair and urine analysis for cocaine and tobacco. - spont. abortion intact preg OR
- cocaine pos. 28.9 20.5 1.4 (1.0-2.1)
- tobacco pos. 34.6 21.8 1.8 (1.3-2.6)