hypertensive disorder of pregnancy

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Hypertensive disorders of pregnancy

Updated 2014 Mar 17 06:49:00 AM: oral nif edipine associated withshorter t ime to target blood pressure compared with IV labetalol inpregnant women with hypertensive emergency (Obstet Gynecol 2013 Nov)view updateShow more updates

General Inf ormation

Descript ion:

hypertension during pregnancy(1, 2, 3, 4)

systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg during pregnancy

may be pre-existing hypertension in woman with chronic hypertension

may be gestational hypertension (new onset af ter 20 weeks gestation)

preeclampsia(1, 2, 3, 4)

typically def ined as hypertension with proteinuria (protein > 300 mg in 24-hour urine specimen)af ter 20 weeks gestation

severe preeclampsia if any of

blood pressure 160/110 mm Hg on 2 occasions at least 6 hours apart during bed rest

proteinuria 5 g/24 hours or 3+ on 2 random urine specimens at least 4 hours apart

cerebral or visual disturbances, including headache

epigastric or right upper quadrant pain

f etal growth restriction

impaired liver f unction

oliguria < 500 mL/24 hours

pulmonary edema

thrombocytopenia

cyanosis

Also called:

preeclampsia

gestational hypertension

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pregnancy- induced hypertension

PIH

toxemia of pregnancy

gestosis

preeclamptic toxemia

gestational hypertension has replaced term pregnancy- induced hypertension(1)

Types:

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definit ions used in American guidelines

chronic hypertension def ined as systolic blood pressure 140 mm Hg or diastolic bloodpressure 90 mm Hg on > 2 occasions bef ore 20 weeks gestation or beyond 12 weekspostpartum(2, 4, 5, 6)

mild - 140-150 mm Hg systolic or 90-109 mm Hg diastolic

severe - 160 mm Hg systolic or 110 mm Hg diastolic

gestational hypertension(1, 4)

replaces term of pregnancy- induced hypertension

hypertension without proteinuria developing af ter 20 weeks gestation

temporary diagnosis - either progresses to preeclampsia or chronic hypertension, orresolves and becomes transient hypertension

transient hypertension - gestational hypertension with normal blood pressure by 12 weekspostpartum(4)

preeclampsia

hypertension (blood pressure 140/90 mm Hg) and proteinuria (> 300 mg/24 hours)af ter 20 weeks gestation(1, 4, 5)

severe preeclampsia is preeclampsia with any of (1, 5)

blood pressure 160/110 mm Hg on 2 occasions at least 6 hours apart duringbed rest

proteinuria 5 g/24 hours or 3+ on 2 random urine specimens at least 4 hoursapart

cerebral or visual disturbances

epigastric or right upper quadrant pain

f etal growth restriction

impaired liver f unction

oliguria < 500 mL/24 hours

pulmonary edema or cyanosis

thrombocytopenia

preeclampsia superimposed on chronic hypertension(4)

in woman with hypertension bef ore 20 weeks gestation - new onset proteinuria

in woman with hypertension and proteinuria bef ore 20 weeks gestation - any of

sudden 2- to 3-f old increase in proteinuria

sudden increase in blood pressure

thrombocytopenia

elevated aspartate aminotransf erase (AST) or alanine aminotransf erase (ALT)

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Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations forclassif ication of hypertensive disorders of pregnancy(3)

hypertension in pregnancy def ined as diastolic blood pressure 90 mm Hg, based on averageof at least 2 measurements using same arm (SOGC Grade B, Level II-2)

severe hypertension def ined as systolic blood pressure 160 mm Hg or diastolic bloodpressure 110 mm Hg (SOGC Grade B, Level II-2)

f or diagnosis of clinically signif icant proteinuria

strongly suspect proteinuria when urinary dipstick proteinuria 2+ (SOGC Grade A,Level II-2)

proteinuria def ined as 0.3 g/day in 24-hour urine collection or 30 mg/mmol urinarycreatinine in spot (random) urine sample (SOGC Grade B, Level II-2)

insuf f icient evidence f or recommendations on accuracy of urinary albumin:creatinineratio (SOGC Grade I, Level II-2)

def init ions of preeclampsia

in women with pre-existing hypertension - resistant hypertension, new or worseningproteinuria, or 1 of other adverse conditions (SOGC Grade B, Level II-2)

in women with gestational hypertension - new-onset proteinuria or 1 of other adverseconditions (SOGC Grade B, Level II-2)

severe preeclampsia def ined as preeclampsia with onset bef ore 34 weeks gestation, withheavy proteinuria or with 1 adverse conditions (SOGC Grade B, Level II-2)

adverse conditions include

maternal symptoms of hypertension such as headache, visual changes, abdominal pain

maternal signs of end-organ dysf unction

abnormal maternal laboratory testing

elevated aspartate aminotransf erase (AST), alanine aminotransf erase (ALT), lactatedehydrogenase (LDH) with symptoms

platelet count < 100 109/L

albumin < 20 g/L

f etal morbidity

Who is most affected:

f or preeclampsia(2, 4)

women with pre-existing chronic hypertension (especially if 4 years)

nulliparas

multiple gestations

women at > 20 weeks gestation

more f requent in women near term

Incidence/Prevalence:

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ynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef6577

hypertensive disorders(1, 2, 3, 5)

most common medical complication of pregnancy

complicate about 5%-8% of pregnancies in United States

about 1% of pregnancies complicated by pre-existing hypertension

increasing number of hypertension-associated delivery hospitalizations in UnitedStates

based on retrospective cohort of 36,537,061 delivery discharges f rom 1998-2006Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project

prevalence of hypertensive disorders among delivery hospitalizations

67.2 per 1,000 deliveries in 1998

81.4 per 1,000 deliveries in 2006

Ref erence - Obstet Gynecol 2009 Jun;113(6):1299

9.8% women have hypertensive disorder in pregnancy in Australia

based on study of 250,173 women and 255,931 inf ants discharged f rom hospitalf ollowing birth in New South Wales between 2000 and 2002

24,517 women (9.8%) had hypertensive disorder including gestational hypertension(4.3%), preeclampsia (4.2%), chronic hypertension (0.6%) and chronic hypertension withsuperimposed preeclampsia (0.3%)

Ref erence - Med J Aust 2005 Apr 4;182(7):332 f ull- text

7% rate of gestational hypertension in 39,615 pregnancies in World Health Organization(WHO) Antenatal Care Trial (Am J Obstet Gynecol 2006 Apr;194(4):921)

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preeclampsia

prevalence of preeclampsia 3.8% in United States in 2010

based on retrospective cohort study

120,000,000 women hospitalized f or delivery f rom 1980 to 2010 in United States wereanalyzed

in 2010, prevalence of

any preeclampsia 3.8%

severe preeclampsia 1.4%

mild preeclampsia 2.5%

Ref erence - BMJ 2013 Nov 7;347:f 6564

median incidence of preeclampsia 3.9%

based on systematic review of 36 studies with 1,699,073 pregnant women

Ref erence - BJOG 2007 Dec;114(12):1477

2.2% rate of preeclampsia in 39,615 pregnancies in WHO Antenatal Care Trial (Am J ObstetGynecol 2006 Apr;194(4):921)

4.2% rate of preeclampsia among 804,448 pregnancies with f irst child, singleton birth af ter 24weeks gestation in Norway between 1967 and 2003 (JAMA 2006 Sep 20;296(11):1357 f ull- text),correction can be f ound in JAMA 2006 Dec 27;296(24):2926

3.8% rate of preeclampsia among 3,494 women giving birth in Norwegian population-basedstudy (BMJ 2007 Nov 10;335(7627):978 f ull- text), editorial can be f ound in BMJ 2007 Nov10;335(7627):945, commentary can be f ound in BMJ 2007 Nov 24;335(7629):1059

higher prevalence among women with hypertension(3, 4)

occurs in about 25% of women with chronic hypertension

develops in about 35% of women with gestational hypertension with onset < 34 weeksgestation

severe preeclampsia (including hemolysis, elevated liver enzymes, low platelets (HELLP) syndromeand eclampsia) expected to occur in 0.39% deliveries

based on case-control study f rom population of 48,865 women delivering in United Kingdom

compared with 4 randomly selected controls f or each case, risk f actors f or severepreeclampsia were age > 34 years, nonwhite ethnic group, past or current hypertension,previous preeclampsia, diabetes, antenatal admission to hospital, multiple pregnancy, andsocial exclusion

Ref erence - BMJ 2001 May 5;322(7294):1089 f ull- text

Causes and Risk Factors

Causes:

cause unknown in most cases of hypertension during pregnancy, especially f or preeclampsia(1)

Pathogenesis:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=24201165&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17903233&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=16580277&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=16985227&http://jama.jamanetwork.com/article.aspx?articleid=203381http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17975256&http://www.bmj.com/content/335/7627/978http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17975257&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18033889&http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8373http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef6577http://web.b.ebscohost.com/dynamed/linklist/GetRecord?sid=3e2bb46a-602f-4975-8177-19f827a86092@sessionmgr198&vid=5&theTerm=AN 167833http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=11337436&http://www.bmj.com/cgi/content/full/322/7294/1089http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8159

reduced organ perf usion due to vasospasm and activation of coagulation cascade (Am J ObstetGynecol 2000 Jul;183(1):S1), commentary can be f ound in Am J Obstet Gynecol 2001 Aug;185(2):522

preeclampsia

abnormal and shallow placentation (due to f ailure of normal trophoblastic invasion of spiralarteries) is hallmark of preeclampsia(2)

hypotheses on pathogenesis

abnormal placental implantation(1)

def ects in trophoblasts

def ects in spiral arterioles

angiogenic f actors(1)

cardiovascular maladaptation and vasoconstriction(1)

genetic predisposit ion (f or example, maternal or paternal thrombophilias)(1)

immunologic intolerance between f etoplacental and maternal t issue(1)

platelet activation(1)

vascular endothelial damage or dysf unction(1, 2, 3)

possible 2-stage process causing mismatch between uteroplacental supply andf etal demands, leading to maternal endothelial cell dysf unction and maternal andf etal manif estations

in f irst stage, placenta produces specif ic proteins or trophoblastic debristhat enter maternal circulation

in second stage, clinical disease dependent on circulating f actors andhealth of mother

endothelial dysf unction implicated in case-control study (JAMA 2001 Mar28;285(12):1607)

mRNA expression of pregnancy-specif ic beta1 glycoprotein and trophoblastglycoprotein increased in study of 5 women with preeclampsia and 5 controls (ObstetGynecol 2007 Nov;110(5):1130)

prostacyclin (PGI2) def iciency implicated (JAMA 1999 Jul 28;282(4):356), commentary canbe f ound in JAMA 2000 Mar 22-29;283(12):1568

increased sympathetic vasoconstrictor activity (N Engl J Med 1996 Nov14;335(20):1480 f ull- text), commentary can be f ound in N Engl J Med 1997 May1;336(18):1326

signif icant structural capillary raref action (Obstet Gynecol 2012 May;119(5):967)

review of pathogenesis and genetics of preeclampsia can be f ound in Lancet 2001 Jan6;357(9249):53

review of uric acid as pathogenic f actor in preeclampsia can be f ound in Placenta 2008 Mar;29Suppl A:S67

Likely risk factors:

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more important risk f actors f or preeclampsia (consider specialty ref erral if 1 f actor present)(1, 3)

maternal age 40 years

medical, f amily and social history

previous preeclampsia, especially if severe or bef ore 32 weeks gestation

f amily history of preeclampsia (mother or sister)

antiphospholipid antibody syndrome

pre-existing hypertension or diastolic blood pressure 90 mm Hg at f irst antenatal visit

pre-existing renal disease or proteinuria at f irst antenatal visit

pre-existing diabetes mellitus

obesity (body mass index 35 kg/m2)

risk f actors in current pregnancy

multiple pregnancy

f irst ongoing pregnancy

interpregnancy interval 10 years

blood pressure 130 mm Hg systolic or 80 mm Hg diastolic at f irst antenatal visit

http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8159http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8373http://web.b.ebscohost.com/dynamed/linklist/GetRecord?sid=3e2bb46a-602f-4975-8177-19f827a86092@sessionmgr198&vid=5&theTerm=AN 115478

less important risk f actors f or preeclampsia (consider special ref erral risk if 2 risk f actorspresent)(1, 3)

demographic risk f actors

lower socioeconomic status

Nordic, Black, South Asian, or Pacif ic Island ethnicity

medical, f amily and social history

heritable thrombophilias

nonsmoking (based on observational studies)

increased prepregnancy triglyceride levels

f amily history of early-onset cardiovascular disease

cocaine and methamphetamine use

risk f actors in current pregnancy

interpregnancy interval < 2 years

use of reproductive technologies

new partner

gestational trophoblastic disease

excessive weight gain in pregnancy

inf ection during pregnancy (f or example, urinary tract inf ection, periodontal disease)

possible risk f actors occurring in second or third trimester of current pregnancy

elevated blood pressure

abnormal maternal serum screening

abnormal uterine artery Doppler velocimetry

cardiac output > 7.4 L/minute

elevated uric acid

http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8159http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8373

evidence regarding specif ic risk f actors

increasing maternal age associated with increased risk of hypertensive disorders ofpregnancy


203,517 women (15% 35 years old) with singleton gestation stratif ied by maternal age

compared with women aged 25-29.9 years, increased risk of hypertensive disorders ofpregnancy in women aged

35-39.9 years (adjusted odds ratio [OR] 1.22, 95% CI 1.12-1.33)

40-44.9 years (adjusted OR 1.63, 95% CI 1.42-1.88)

45 years (adjusted OR 1.89, 95% CI 1.21-2.96)

Ref erence - Obstet Gynecol 2013 Dec;122(6):1184

estimated relative risks for multiple risk factors for preeclampsia

based on systematic review of 48 controlled cohort studies

previous history of preeclampsia (relative risk [RR] 7.19, 95% CI 5.85-8.83)

antiphospholipid antibodies (RR 9.72, 95% CI 4.34-21.75)

pre-existing diabetes (RR 3.56, 95% CI 2.54-4.99)

multiple gestations (RR 2.93, 95% CI 2.04-4.21)

nulliparity (RR 2.91, 95% CI 1.28-6.61)

f amily history (RR 2.9, 95% CI 1.7-4.93)

diastolic blood pressure 80 mm Hg (RR 1.38, 95% CI 1.01-1.87)

increased body mass index bef ore pregnancy (RR 2.47, 95% CI 1.66-3.67) or atpresentation (RR 1.55, 95% CI 1.28-1.88)

maternal age > 40 years (RR 1.96, 95% CI 1.34-2.87) f or multiparous women

additional possible risk f actors based on individual studies

interval 10 years since previous pregnancy

autoimmune disease

renal disease

chronic hypertension

Ref erence - BMJ 2005 Mar 12;330(7491):565 f ull- text, editorial can be f ound in BMJ2005 Mar 12;330(7491):549

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=24201681&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list%5Fuids=15743856&dopt=Abstract&http://www.bmj.com/content/330/7491/565.fullhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=15760971&

adjusted odds ratios for multiple risk factors for preeclampsia

based on prospective cohort study of 3,572 healthy, nulliparous women with singletonpregnancy

preeclampsia in 5.3%

clinical risk f actors at 15 weeks gestation f or preeclampsia

f amily history of preeclampsia (adjusted odds ratio [OR] 2, 95% CI 1.3-3)

vaginal bleeding 5 days (adjusted OR 2, 95% CI 1.1-3.8)

f amily history of coronary artery disease (adjusted OR 1.9, 95% CI 1.2-2.8)

increase of 5 mm Hg in mean arterial pressure (calculated at 14-16 weeksgestation) (adjusted OR 1.4, 95% CI 1.3-1.5)

Ref erence - BMJ 2011 Apr 7;342:d1875 f ull- text

circulatory risk profile appears common in women with history of preeclampsia


1,234 f ormerly preeclamptic nonpregnant women screened f or 4 possible risk prof iles(circulatory [hypertension or latent hypertension], metabolic syndrome, thrombophilia[f actor V Leiden, prothrombin mutation, or protein C or S def iciency], andhyperhomocysteinemia) 6-12 months postpartum

77.6% had 1 risk prof ile

risk prof ile prevalence

circulatory 66.1%

metabolic syndrome 15.4%

thrombophilia 10.8%

hyperhomocysteinemia 18.7%

prevalence of circulatory, metabolic syndrome, and hyperhomocysteinemia risk prof ilesdecreased signif icantly with gestational age at delivery

minimal overlap occurred between metabolic syndrome, thrombophilic, andhyperhomocysteinemia risk prof iles

Ref erence - Obstet Gynecol 2013 Jan;121(1):97

risk factors for new-onset late postpartum preeclampsia

based on case-control study

34 women with new-onset late postpartum preeclampsia (LPP) af ter normal delivery and68 women without new-onset LPP matched by delivery date were evaluated

increased risk of new-onset LPP associated with

aged 40 years (adjusted odds ratio [OR] 24.83, p = 0.03)

Black race (adjusted OR 78.35, p < 0.001)

Latino ethnicity (adjusted OR 19.08, p = 0.01)

gestational diabetes (adjusted OR 72.91, p < 0.001)

Ref erence - Am J Obstet Gynecol 2013 Nov 7 early online

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21474517&http://www.bmj.com/content/342/bmj.d1875.longhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23262933&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=24211478&

additional risk f actors and subsequent studies include

obesity as risk factor supported by multiple subsequent studies

multiple gestation associated with increased risk of pregnancy-relatedhypertensive disease

based on cohort of 34,374 pregnancies with 1-4 f etuses with no hypertension atprenatal booking and delivery af ter 28 weeks gestation

incidence of pregnancy-related hypertensive conditions 6.5% f or singletonpregnancies vs. 12.7%-19.6% f or multif etal pregnancies (p < 0.001)

incidence of severe pregnancy-related hypertensive conditions (hemolysis,elevated liver enzymes, low platelets [HELLP] syndrome, disseminatedintravascular coagulation, eclampsia, low platelets, renal f ailure, abruption) was0.5% f or singleton pregnancies vs. 1.6% f or twin and 3.1% f or triplet pregnancies(p < 0.001)

independent risk f actors f or pregnancy-related hypertensive conditions wereincreasing f etal number, nulliparity, and advanced maternal age

Ref erence - Obstet Gynecol 2005 Nov;106(5):927

preterm delivery in sett ing of preeclampsia and low fetal growth associated withincreased risk of preeclampsia in subsequent pregnancy

based on retrospective cohort of 536,419 women with f irst and second singletondeliveries in Denmark f rom 1978 to 2007


rheumatologic disease associated with higher risk of preeclampsia

based on cohort of 114 mothers with rheumatologic disease (systemic lupuserythematosus, rheumatoid arthrit is, antiphospholipid antibody syndrome, orother rheumatologic disease) vs. 18,534 mothers without rheumatologic disease


migraine headaches associated with increased risk of hypertensive disorders inpregnancy

based on prospective cohort of 702 normotensive women with singletonpregnancy at 11-16 weeks gestation

migraine diagnosis in 38.5%

hypertensive disorder developed in 9.1% women with migraines vs. 3.1% withoutmigraines (adjusted odds ratio 2.85, p < 0.05)

Ref erence - Cephalalgia 2009 Mar;29(3):286

prepregnancy lipid and blood pressure levels associated with risk forpreeclampsia

higher maternal triglyceride levels may be associated with higher risk forpreeclampsia

based on systematic review of 5 cohort studies and 24 case-control studies

Ref erence - BJOG 2013 Oct;120(11):1321

http://web.b.ebscohost.com/dynamed/linklist/GetRecord?sid=3e2bb46a-602f-4975-8177-19f827a86092@sessionmgr198&vid=5&theTerm=AN 167833http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=16260508&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19461415&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list%5Fuids=15172851&dopt=Abstract&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19220309&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23859707&

microalbuminuria or nephropathy associated with increased risk of preterm laborand preeclampsia in women with diabetes mellitus type 1

based on cohort of 240 pregnant women with diabetes mellitus type 1

Ref erence - Diabetes Care 2001 Oct;24(10):1739

women born small for gestational age are at higher risk for preeclampsia

based on population-based cohort study of 118,634 women registered asnewborns and as mothers in Sweden

Ref erence - BJOG 2007 Mar;114(3):319

some antidepressants used during pregnancy associated with increased risk ofpreeclampsia but not selective serotonin reuptake inhibitors(level 2 [mid-level] evidence)


69,448 pregnant women with depression had no treatment or monotherapy with selectiveserotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), ortricyclic antidepressants (TCAs)

risk of preeclampsia increased with use of SNRIs and TCAs

use during gestational weeks 10-20 (vs. no antidepressant use)

SNRIs (adjusted relative risk [RR] 1.95, 95% CI 1.25-3.03)

TCAs (adjusted RR 3.23, 95% CI 1.87-5.59)

use during gestational weeks 10-24 among women with pre-pregnancy antidepressantuse (vs. discontinued use during gestational weeks 10-24)

SNRIs (adjusted RR 3.43, 95% CI 1.77-6.65)

TCAs (adjusted RR 3.26, 95% CI 1.04-10.24)

no signif icant dif f erences with use of SSRIs

Ref erence - Am J Epidemiol 2012 May 15;175(10):988

genetic predisposit ion

mother, aunt or paternal grandmother with preeclampsia associated with increasedrisk of preeclampsia

based on population-based study of linked generational data f rom Norway with 438,597mother-of f spring pairs and 286,945 f ather-of f spring pairs

Ref erence - BMJ 2005 Oct 15;331(7521):877 f ull- text

genetic predisposit ion comes f rom both mother and f ather (f etus f rom f ather who f athered apreeclamptic pregnancy increases risk) (BMJ 1998 May 2;316(7141):1343 f ull- text)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=11574435&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17261123&http://www.epnet.com/dynamed/levels.phphttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=22442287&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list%5Fuids=16169871&dopt=Abstract&http://www.bmj.com/cgi/content/full/331/7521/877http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=9563982&http://www.bmj.com/cgi/content/full/316/7141/1343

interpregnancy interval

interpregnancy interval > 59 months associated with increased risk for preeclampsiaand eclampsia

based on 456,889 women delivering singleton inf ants between 1985 and 1997

pregnancy interval > 59 months in 19.5%

Ref erence - BMJ 2000 Nov 18;321(7271):1255

increasing interpregnancy interval associated with increasing risk for preeclampsia

based on study of 551,478 women with 2 singleton deliveries and 209,423 women with 3singleton deliveries

preeclampsia in 3.9% with f irst pregnancy, 1.7% with second pregnancy and 1.8% withthird pregnancy

if > 10 years, odds ratio f or preeclampsia 1.12 f or each 1-year increase in interbirthinterval

Ref erence - N Engl J Med 2002 Jan 3;346(1):33, commentary can be f ound in N Engl JMed 2002 Jun 6;346(23):1831

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=11082085&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list%5Fuids=11778000&dopt=Abstract&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=12050350&

periodontal disease may be associated with increased risk of preeclampsia, but evidenceinconsistent

periodontit is during pregnancy not associated with preeclampsia in 1 cohort study


786 pregnant women with periodontal exam < 20 weeks gestation evaluatedretrospectively f ollowing delivery

311 women with periodontal disease

475 women without periodontal disease

preeclampsia def ined as hypertension (blood pressure 140/90 mm Hg) with proteinuriaaf ter 20 weeks gestation

periodontal disease not associated with preeclampsia (adjusted odds ratio 0.71, 95% CI0.37-1.36, p = 0.3)

preeclampsia associated with chronic hypertension (adjusted odds ratio 3.54, 95% CI1.48-8.48, p < 0.005)

Ref erence - Am J Obstet Gynecol 2009 May;200(5):497e1

active periodontal disease during pregnancy associated with increased risk ofpreeclampsia in 1 cohort study

1,115 healthy pregnant women enrolled bef ore 26 weeks gestation, periodontal examsdone at enrollment and within 48 hours of delivery

preeclampsia def ined as blood pressure > 140/90 mm Hg on 2 occasions andproteinuria on catheterized urine at least once

analysis based on 763 women who delivered live inf ants and had data available

39 (5.1%) had preeclampsia

severe periodontal disease associated with 2.1-2.4 times risk of preeclampsia

based on exam bef ore 26 weeks gestation, risk of preeclampsia at t ime of delivery was

2% if healthy gums

5% if mild periodontal disease

6% if severe periodontal disease

based on exam at t ime of delivery, risk of preeclampsia was

3% if healthy gums

5% if mild periodontal disease

10% if severe periodontal disease

Ref erence - Obstet Gynecol 2003 Feb;101(2):227

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19375568&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list%5Fuids=12576243&dopt=Abstract&

periodontal disease and urinary tract infection during pregnancy may be associatedwith increased risk of preeclampsia

based on systematic review with heterogeneity

systematic review of 49 cohort, cross-sectional and case-control studies

periodontal disease associated with preeclampsia (odds ratio 1.76, 95% CI 1.43-2.18) in6 studies with high degree of heterogeneity (I2 = 79%)

urinary tract inf ection associated with preeclampsia (odds ratio 1.57, 95% CI 1.45-1.70)in 17 studies with high degree of heterogeneity (I2 = 80%)

no association f ound with HIV inf ection, malaria, or presence of antibodies toChlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus

Ref erence - Am J Obstet Gynecol 2008 Jan;198(1):7, commentary can be f ound in EvidBased Dent 2008;9(2):46

Possible risk factors:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18166297&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18584002&

anticardiolipin antibodies, MTHFR homozygosity, and hyperhomocysteinemia may increase risk f orpreeclampsia but evidence conf licting f or women with mutations in f actor V Leiden or prothrombinG20210A

moderate-to-high levels of anticardiolipin antibodies may be associated withpreeclampsia

based on systematic review of observational studies limited by heterogeneity

systematic review of 12 studies (cohorts, case-controls, or cross-sectional studies)evaluating association of anticardiolipin antibodies and preeclampsia

moderate-to-high levels of anticardiolipin antibodies associated with

preeclampsia (odds ratio [OR] 2.86, 95% CI 1.37-5.98) in analysis of 12 studies(results limited by heterogeneity)

severe preeclampsia (OR 11.15, 95% CI 2.66-46.75) in analysis of 5 studies(results limited by heterogeneity)


factor V Leiden heterozygosity, prothrombin heterozygosity, MTHFR homozygosity,anticardiolipin antibodies, and hyperhomocysteinemia each associated withpreeclampsia

based on systematic review of trials with signif icant heterogeneity and observationalstudies

systematic review of 79 randomized trials or observational studies (prospective orretrospective) evaluating pregnant women or women up to 6 weeks postpartum withthrombophilia

compared to women without thrombophilia, risk f or preeclampsia increased with

f actor V Leiden heterozygosity (odds ratio [OR] 2.19, 95% CI 1.46-3.27) inanalysis of 14 studies with 3,922 patients (results limited by signif icantheterogeneity)

prothrombin heterozygosity (OR 2.54, 95% CI 1.52-4.23) in analysis of 8 studieswith 2,099 patients

methylenetetrahydrof olate reductase enzyme (MTHFR) homozygosity (OR 1.37,95% CI 1.07-1.76) in analysis of 12 studies with 3,686 patients

anticardiolipin antibodies (OR 2.73, 95% CI 1.65-4.51) in analysis of 8 studies with2,645 patients

hyperhomocysteinemia (OR 3.49, 95% CI 1.21-10.11) in analysis of 2 studies with405 patients

Ref erence - Br J Haematol 2006 Jan;132(2):171

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21099614&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=16398652&

mutations in factor V Leiden and prothrombin G20210A may not be associated withpreeclampsia

based on systematic review of observational studies

systematic review of 10 prospective cohort studies comparing pregnancy complicationsin pregnant women with prothrombin gene mutation or f actor V Leiden with womenwithout these conditions

review limited by heterogeneity due to baseline dif f erences in study populations

compared to women without thrombophilia, no signif icant dif f erence in risk f orpreeclampsia

f actor V Leiden (homozygous or heterozygous) in analysis of 9 studies with21,833 women

prothrombin G20210A mutation (homozygous or heterozygous) in analysis of 6studies with 14,254 women

Ref erence - PLoS Med 2010 Jun 15;7(6):e1000292 f ull- text

see Thrombophilia in pregnancy f or details

in utero diethylstilbestrol (DES) exposure associated with preeclampsia

based on 2 cohort studies

cohort study of 7,313 live births, including 4,759 with in utero DES exposure

incidence of preeclampsia was 4.4% in DES exposed and 2.9% DES unexposedpregnancies

Ref erence - Obstet Gynecol 2007 Jul;110(1):113

retrospective cohort study of 4,653 women exposed to DES in utero and 1,927 women withoutDES exposure

DES exposure associated with increased risk of preeclampsia compared to no exposure(26.4% vs. 13.7%, p < 0.05)

Ref erence - N Engl J Med 2011 Oct 6;365(14):1304

vitamin D insufficiency during pregnancy associated with increased risk of preeclampsia

based on systematic review

systematic review of 31 observational studies evaluating association between maternal serum25-hydroxyvitamin D level during pregnancy, and pregnancy and neonatal outcomes

insuf f icient maternal serum 25-hydroxyvitamin D level associated with increased risk ofpreeclampsia (odds ratio 1.79, 95% CI 1.25-2.58) in analysis of 7 studies

Ref erence - BMJ 2013 Mar 26;346:f 1169 f ull- text, similar results f ound in systematic review of15 observational studies evaluating association between serum 25-hydroxyvitamin D levelduring pregnancy and risk of preeclampsia (J Clin Endocrinol Metab 2013 Aug;98(8):3165-73)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=20563311&http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885985/?tool=pubmedhttp://web.b.ebscohost.com/dynamed/linklist/GetRecord?sid=3e2bb46a-602f-4975-8177-19f827a86092@sessionmgr198&vid=5&theTerm=AN 901060http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17601905&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21991952&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23533188&http://www.bmj.com/content/346/bmj.f1169?view=long&pmid=23533188http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23783101&

secondary hyperparathyroidism plus low vitamin D level associated with increased risk ofpreeclampsia


1,141 pregnant women of low-income and minority status were analyzed

presence of secondary hyperparathyroidism plus 25-hydroxyvitamin D < 20 ng/mL associatedwith increased risk of preeclampsia (adjusted odds ratio 2.86, 95% CI 1.28-6.41)

Ref erence - Am J Clin Nutr 2013 Sep;98(3):787

polycystic ovary syndrome associated with increased risk for gestational diabetes,preeclampsia, and preterm delivery

based on systematic review of cohort studies and additional large cohort study

systematic review of 23 cohort studies (8 prospective, 15 retrospective) reporting associationbetween polycystic ovary syndrome and pregnancy outcomes in 2,544 women with polycysticovary syndrome and 89,848 women without polycystic ovary syndrome

polycystic ovary syndrome associated with increased risk of

gestational diabetes (odds ratio [OR] 2.8, 95% CI 1.9-4)

pregnancy- induced hypertension (OR 4, 95% CI 2.8-6)

preeclampsia (OR 4.2, 95% CI 2.8-6.5)

preterm delivery (OR 2.2, 95% CI 1.6-3)

inf ants born to mothers with polycystic ovary syndrome had increased risk of small- f or-gestational-age (OR 2.62, 95% CI 1.35-5.1)

no signif icant association between polycystic ovary syndrome and cesarean delivery,operative vaginal delivery, and birth of large-f or-gestational-age inf ants

Ref erence - Am J Obstet Gynecol 2011 Jun;204(6):558.e1

prospective cohort study comparing 3,787 births among women with polycystic ovarysyndrome and 1,191,336 births among women without polycystic ovary syndrome

polycystic ovary syndrome associated with increased risk of

preeclampsia (adjusted odds ratio [OR] 1.45, 95% CI 1.24-1.69)

very preterm birth (adjusted OR 2.21, 95% CI 1.69-2.9)

gestational diabetes (adjusted OR 2.32, 95% CI 1.88-2.88)

inf ants born to mothers with polycystic ovary syndrome had increased risk of

being large f or gestational age (adjusted OR 1.39, 95% CI 1.19-1.62)

meconium aspiration (adjusted OR 2.02, 95% CI 1.13-3.61)

low Apgar score (< 7) at 5 minutes (adjusted OR 1.41, 95% CI 1.09-1.83)

Ref erence - BMJ 2011 Oct 13;343:d6309 f ull- text, editorial can be f ound in BMJ 2011Oct 13;343:d6407

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23885046&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21752757&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21998337&http://www.bmj.com/content/343/bmj.d6309?view=long&pmid=21998337http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21998338&

increase of 3 BMI units between f irst and second pregnancies associated with increasedrisk of pregnancy-induced hypertension in normal and underweight women

based on cohort study

7,897 women with f irst 2 consecutive deliveries between 2009 and 2011 evaluated f orinterpregnancy weight change (dif f erence between prepregnancy body mass indices [BMI] off irst and second pregnancies)

f or normal and underweight women only, increase in interpregnancy interval by 3 BMI unitsassociated with increased risk of pregnancy- induced hypertension (adjusted odds ratio 3.76,95% CI 2.16-6.57)


subclinical hypothyroidism may increase risk of hypertensive disorders in pregnancy

based on prospective cohort study

24,883 women who delivered a singleton inf ant were assessed f or hypertension in pregnancy

2.1% had subclinical hypothyroidism

overall incidence of hypertensive disorders in pregnancy

10.9% in patients with subclinical hypothyroidism (p = 0.016 vs. other groups)

6.2% in patients with subclinical hyperthyroidism

8.5% in euthyroid patients

subclinical hypothyroidism associated with increased risk of severe preeclampsia (adjustedodds ratio 1.6, 95% CI 1.1-2.4)

Ref erence - Obstet Gynecol 2012 Feb;119(2 Pt 1):315

higher HbA1c associated with increased risk of preeclampsia in women with type 1 diabetes

based on prospective cohort analysis of DAPIT trial

127 (17% of original trial) women with type 1 diabetes had preeclampsia and 83 (11%) hadgestational hypertension

preeclampsia associated with higher HbA1c bef ore and during pregnancy (p < 0.05 vs. nopreeclampsia development)

HbA1c 8% in early pregnancy increased risk of preeclampsia (odds ratio [OR] 3.68, 95% CI1.17-11.6) (vs. HbA1c 6.1% as optimal control)

increased risk of preeclampsia at 26 weeks gestation with (vs. HbA1c < 6.1%)

HbA1c 6.1%-6.9% (OR 2.09, 95% CI 1.03-4.21)

HbA1c 7%-7.9% (OR 3.2, 95% CI 1.47-7)

HbA1c 8% (OR 3.81, 95% CI 1.3-11.1)

increased risk of preeclampsia at 34 weeks gestation (vs. HbA1c < 6.1%)

HbA1c 7%-7.9% (OR 3.27, 1.31-8.2)

HbA1c 8% (OR 8.01, 2.04-31.5)

no signif icant association of glycemic control with gestational hypertension risk

Ref erence - Diabetes Care 2011 Aug;34(8):1683

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=24104777&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=22270283&http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#rev3x116522http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21636798&

angiogenesis-related biomarkers associated with risk of preeclampsia

elevated levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and reduced levels ofplacental growth factor (PlGF)

other maternal serum angiogenesis-related biomarkers associated with preeclampsia in case-control study comparing 40 women with preeclampsia and 100 controls

increased soluble endoglin (sEng)

increased ratio sFlt-1/placental growth f actor (PlGF)

increased ratio soluble endoglin/transf orming growth f actor-beta1 (TGF-beta1)

increased combined ratio of (sFlt-1 + soluble endoglin)/(PlGF + TGF-beta1)

decreased TGF-beta1

Ref erence - Obstet Gynecol 2008 Jun;111(6):1403, correction can be f ound in ObstetGynecol 2008 Sep;112(3):710

elevated plasma kynurenic acid may be associated with increased risk of preeclampsia


2,936 women with singleton pregnancies evaluated f or six kynurenine pathway metabolites atapproximately 18 weeks gestation

4% subsequently developed preeclampsia

kynurenic acid concentration > 95th percentile associated with increased risk of preeclampsiacompared to kynurenic acid concentration in 25th-75th percentile (adjusted odds ratio 3.6,95% CI 1.9-6.8)Ref erence - Obstet Gynecol 2012 Jun;119(6):1243

HLA-DR genotypes (particularly DR4) may be associated with preeclampsia risk

based on systematic review of 22 studies of HLA allele f requencies in association withpreeclampsia or intrauterine growth retardation

9 of 10 studies suggested DR allelic dif f erences associated with preeclampsia

2 of 3 studies suggested no association between HLA alleles and intrauterine growthretardation

6 studies of HLA homozygosity as risk f actor f or preeclampsia had mixed results

Ref erence - Obstet Gynecol 2005 Jul;106(1):162

cytokine genotype associated with preeclampsia in case-control study of 150 primiparouspreeclamptic women and 661 primiparous normotensive women (Am J Obstet Gynecol 2005Jul;193(1):209)

plasma adiponectin levels < 6.4 mcg/mL associated with hypertensive disorders inpregnancy, especially preeclampsia, in case-control study (Obstet Gynecol 2005 Aug;106(2):340)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18515525&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=22617590&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=15994633&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=16021081&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=16055585&

history of fert ility treatment and recurrent miscarriage may be associated with increasedrisk of preeclampsia in pregnant nulliparous women

based on cohort study in Norway

20,846 nulliparous women with singleton pregnancies completed questionnaires onmiscarriage and inf ertility

preeclampsia diagnosis retrieved f rom national registry

preeclampsia associated with

recurrent miscarriage and f ertility treatment (p < 0.05)

f ertility treatment (p < 0.05)

recurrent miscarriage (not signif icant)

Ref erence - BJOG 2009 Jan;116(1):108

in vitro fert ilization with donor egg associated with increased risk of gestationalhypertension and preeclampsia compared with autologous in vitro fert ilization


158 pregnancies resulting f rom donor egg or autologous in vitro f ertilization (IVF) wereevaluated

comparing donor ovum vs. autologous IVF

gestational hypertension in 24.7% vs. 7.4% (p < 0.01)

preeclampsia in 16.9% vs. 4.9% (p = 0.02)

premature delivery in 34.2% vs. 19% (p = 0.03)


Factors not associated with increased risk:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19087081&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21099607&

smoking

smoking in pregnancy associated with decreased risk of preeclampsia in youngerwomen without pregestational hypertension

based on cohort study of 674,250 singleton pregnancies in New York City f rom 1995-2003

smoking associated with overall reduced risk of preeclampsia (adjusted odds ratio 0.88,p < 0.05) with greatest ef f ect observed in women 30 years

smoking not associated with reduced risk of preeclampsia in women with chronichypertension (adjusted odds ratio 1.04, p > 0.05)

Ref erence - Am J Epidemiol 2009 Jan 1;169(1):33

moderate smoking during pregnancy (1-9 cigarettes/day) associated with DECREASEDrisk of preeclampsia in retrospective analysis of 127,721 singleton pregnancies, reasonsunknown (Acta Obstet Gynecol Scand 1999 Sep;78(8):693)

smoking during pregnancy in overweight and obese women may not protect againstpreeclampsia

based on retrospective cohort of 7,757 healthy primigravid women with singletonpregnancies between 1959 and 1965

smoking decreased risk of preeclampsia in underweight and normal weight women

Ref erence - Am J Epidemiol 2008 Aug 15;168(4):427 f ull- text

history of abortion or preterm birth does not increase risk of preeclampsia compared tonulliparous women

based on retrospective study of 140,773 pregnancies

history of term pregnancy decreases risk

Ref erence - Am J Obstet Gynecol 2002 Oct;187(4):1013 in JAMA 2003 Jan 15;289(3):280

psychosocial stress before 24 weeks gestation does not appear associated with increasedincidence of preeclampsia or gestational hypertension during f irst pregnancy

based on cohort study with low completion rates

3,679 nulliparous women pregnant with singleton pregnancy completed questionnaires onsociodemographic and psychosocial f actors bef ore 24 weeks gestation

preeclampsia in 3.5%

gestational hypertension in 4.4%

no association observed between preeclampsia or gestational hypertension and work stress,anxiety, pregnancy-related anxiety or depression

Ref erence - BJOG 2008 Apr;115(5):607

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19001134&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=10468061&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18558661&http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18558661http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list%5Fuids=12388998&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18333942&

inhaled corticosteroids not associated with increased risk of pregnancy-inducedhypertension

based on case control study

302 cases of pregnancy- induced hypertension (including 165 cases of preeclampsia)compared with 3,013 matched controls (including 1,643 matched controls f or preeclampsiacomparison)

no signif icant dif f erences in either outcome with adjusted odds ratios about 1

oral corticosteroids were associated with

increased risk f or pregnancy- induced hypertension (adjusted odds ratio 1.57, 95% CI1.02-2.41)

trend f or preeclampsia (adjusted odds ratio 1.72, 95% CI 0.98-3.02)

Ref erence - BMJ 2005 Jan 29;330(7485):230 f ull- text

serum folate levels in early pregnancy appear high and similar in normotensive andhypertensive pregnant women exposed to folic acid supplementation

based on nested case-control study

214 pregnant women who developed a hypertensive disorder of pregnancy compared with 428similar normotensive pregnant women

> 98% took f olic acid supplement 0.4-2 mg daily bef ore the end of the f irst trimester

no patients considered f olate def icient (< 10 nmol/L)

mean serum f olate level 60.1 nmol/L in women with hypertensive disorder vs. 57.9 nmol/L incontrols (not signif icant)

Ref erence - Obstet Gynecol 2013 Aug;122(2 Pt 1):345

angiotensin-1 converting enzyme gene (ACD-I/D) variant not likely to affect risk ofpreeclampsia

no signif icant association in large case-control study with 665 cases and 1,046 healthypregnant controls

signif icant association in meta-analysis of 22 studies with 2,596 cases and 3,828 controls, butsignif icant dif f erences mostly attributed to smaller studies

Ref erence - PLoS Med 2006 Dec;3(12):e520 f ull- text

Complications and Associated Conditions

Complicat ions:

Eclampsia:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list%5Fuids=15659480&dopt=Abstract&http://www.bmj.com/cgi/content/full/330/7485/230http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=23969804&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=17194198&http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030520http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#

eclampsia (generalized seizures) - convulsive stage of preeclampsia(1, 2, 3)

may be lif e- threatening

eclamptic seizures may f ollow increasingly severe preeclampsia or occur unexpectedly inpatients with no apparent or minimally elevated blood pressure and no proteinuria

of ten preceded by premonitory signs, such as headache, visual disturbances, epigastric pain,constricting sensation in thorax, apprehension, excitability and hyperref lexia

most convulsions occur prepartum, intrapartum or 48 hours postpartum

seizures usually isolated

neuroimaging may show ischemia with edema

rate of eclampsia 0.38 per 1,000 deliveries in Canada f rom 1991 to 2001 based on 973 cases, 4deaths (0.4% case f atality rate) (CMAJ 2005 Sep 27;173(7):759 f ull- text)

incidence of eclampsia 6.2 per 10,000 deliveries with case f atality 1 in 74 in the Netherlands f rom2004 to 2006 based on cohort study of 371,021 pregnancies (Obstet Gynecol 2008 Oct;112(4):820)

postpartum eclampsia complicated by brain edema and ischemic and hemorrhagic strokes in casepresentation (N Engl J Med 2009 Mar 12;360(11):1126)

late postpartum eclampsia can occur f rom 48 hours to several weeks af ter delivery

90% of postpartum eclampsia cases occur within 7 days of delivery discharge

based on retrospective cohort study of 152 women meeting criteria f or diagnosis ofdelayed postpartum preeclampsia at > 2 days to 6 weeks f ollowing delivery

no preceding diagnosis of hypertensive disorder in 63.2%

headache was most common presenting symptom (69.1%)

postpartum eclampsia

developed in 22 patients (14.5%)

90% of cases presented within 7 days of discharge af ter delivery

mean age 23 years in patients who developed eclampsia vs. 28 years in patients withouteclampsia (p = 0.03)


Maternal complicat ions:

possible maternal complications include(1, 2, 3)

http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8159http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef7796http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8373http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=16186582&http://www.cmaj.ca/cgi/content/full/173/7/759http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18827124&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=19279345&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21979459&http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef8159http://web.b.ebscohost.com/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes-and-Risk-Factors,sec-Complications-and-Associated-Conditions,sec-History-and-Physical,sec-Diagnosis,sec-Treatment,sec-Prognosis,sec-Prevention-and-Screening,sec-Guidelines-and-Resources,sec-Patient-Information,sec-ICD-9-ICD-10-Codes,sec-References&viewtype=standalone&vid=5&sid=3e2bb46a-602f-4975-8177-19f827a86092%40sessionmgr198&hid=121&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#GenRef77

hypertensive disorder of pregnancy

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