Amniotic fl uid embolism: analysis of the national registry... In the National Registry analysis, the authors suggested that the term “ amniotic fl uid embolism ” be discarded and the sy
Trang 1AFE Although disputed on statistical grounds by Morgan [1] , this misconception persisted in some writings until recently The historic anecdotal association between hypertonic uterine con-tractions and the onset of symptoms in AFE was further clarifi ed
by the analysis of the National Registry [5] These data demon-strated that the hypertonic contractions commonly seen in asso-ciation with AFE appear to be a result of the release of catecholamines into the circulation as part of the initial human hemodynamic response to any massive physiologic insult Under these circumstances, norepinephrine, in particular, acts as a potent uterotonic agent [5,55] Thus, while the association of hypertonic contractions and AFE appears to be valid, it is the physiologic response to AFE that causes the hypertonic uterine activity rather than the converse Indeed, there is a complete ces-sation of uterine blood fl ow in the presence of even moderate uterine contractions; thus, a tetanic contraction is the least likely time during an entire labor process for any exchange between maternal and fetal compartments [56] Oxytocin is not used with increased frequency in patients suffering AFE compared with the general population, nor does oxytocin - induced hyperstimulation commonly precede this condition [5] Thus, several authorities, including the American College of Obstetricians and Gynecologists, have concluded that oxytocin use has no relationship to the occurrence of AFE [1,5,57] A recent population - based cohort study of approximately 3 million deliveries in Canada reported a statistically signifi cant association of labor induction with AFE [58] , however the same investigators did not observe this associa-tion in another populaassocia-tion - based cohort of approximately 3 million deliveries in the US [59] , casting doubt regarding any clinically signifi cant relationship between labor stimulation and AFE
The syndrome of AFE appears to be initiated after maternal intravascular exposure to various types of fetal tissue Such expo-sure may occur during the course of normal labor and delivery; after potentially minor traumatic events, such as appropriate intrauterine pressure catheter placement; or during cesarean section Because fetal - to - maternal tissue transfer is virtually uni-versal during the labor and delivery process, actions by healthcare providers, such as intrauterine manipulation or cesarean delivery, may affect the timing of the exposure No evidence exists, however, to suggest that exposure itself can be avoided by altering clinical management Simple exposure of the maternal circula-tory system to even small amounts of amniotic fl uid or other fetal tissue may, under the right circumstances, initiate the syndrome
of AFE This understanding explains the well - documented occur-rence of fatal AFE during fi rst - trimester pregnancy termination
at a time when neither the volume of fl uid nor positive intrauter-ine pressure could be contributing factors [11] Whereas much has been written about the importance to the fetus of an immu-nologic barrier between the mother and the antigenically differ-ent products of conception, little attdiffer-ention has been paid to the potential importance of this barrier to maternal well - being The observations of the National Registry as well as cumulative data for the past several decades suggest that breaches of this barrier
identical; fever is unique to septic shock, and cutaneous
manifes-tations are more common in anaphylaxis Nevertheless, the
marked similarities of these conditions suggest similar
patho-physiologic mechanisms
Detailed discussions of the pathophysiologic features of septic
shock and anaphylactic shock are presented elsewhere in this text
Both of these conditions involve the entrance of a foreign
sub-stance (bacterial endotoxin or specifi c antigens) into the
circula-tion, which then results in the release of various primary and
secondary endogenous mediators (Figure 35.3 ) Similar
patho-physiology has also been proposed in non - pregnant patients with
pulmonary fat embolism It is the release of these mediators that
results in the principal physiologic derangements characterizing
these syndromes These abnormalities include profound
myocar-dial depression and decreased cardiac output, described in both
animals and humans; pulmonary hypertension, demonstrated in
lower primate models of anaphylaxis; and disseminated
intervas-cular coagulation, described in both human anaphylactic
reac-tions and septic shock [44 – 53] Further, the temporal sequence
of hemodynamic decompensation and recovery seen in
experi-mental AFE is virtually identical to that described in canine
ana-phylaxis [49] An anaphylactoid response is also well described in
humans and involves the non - immunologic release of similar
mediators [44] It is also intriguing that, on admission to hospital,
41% of patients in the AFE registry gave a history of either drug
allergy or atopy [5]
The ability of arachidonic acid metabolites to cause the same
physiologic and hemodynamic changes observed in human AFE
has been noted [54] Further, in the rabbit model of AFE,
pre-treatment with an inhibitor of leukotriene synthesis has been
shown to prevent death [28] These experimental observations
further support the clinical conclusions of the National AFE
Registry analysis that this condition involves the anaphylactoid
release of endogenous mediators, including arachidonic acid
metabolites, which result in the devastating pathophysiologic
sequence seen in clinical AFE [5]
Earlier anecdotal reports suggested a possible relationship
between hypertonic uterine contractions or oxytocin use and
Figure 35.3 Proposed pathophysiologic relation between AFE, septic shock,
and anaphylactic shock Each syndrome also may have specifi c direct physiologic
effects (Reproduced by permission from Clark SL, Hankins GVD, Dudley DA et al
Amniotic fl uid embolism: analysis of the national registry Am J Obstet Gynecol
1995; 172: 1158 – 1169.)
Trang 2opment of a consumptive coagulopathy, which may lead to exsanguination, even if attempts to restore hemodynamic and respiratory function are successful It must be emphasized, however, that in any individual patient any of the three principal phases (hypoxia, hypotension, or coagulopathy) may either dom-inate or be entirely absent [5,38,61] Clinical variations in this syndrome may be related to variations in either the nature of the antigenic exposure or maternal response The differential diag-nosis is summarized in Table 35.3
Maternal outcome is dismal in patients with AFE syndrome
In documented “ classic ” cases, the overall maternal mortality rate appears to be 60 – 80% [5,32] Only 15% of patients survive neu-rologically intact In a number of cases, following successful hemodynamic resuscitation and reversal of disseminated intra-vascular coagulation, life - support systems were withdrawn because of brain death resulting from the initial profound hypoxia In patients progressing to cardiac arrest, only 8% survive neurologically intact [5] In the National Registry database, no form of therapy appeared to be consistently associated with improved outcome A large series of patients in whom the diag-nosis of AFE was obtained from the discharge summary reported
a 26% mortality rate Notably, however, many patients in this series lacked one or more potentially lethal clinical manifestation
of the disease classically considered mandatory for diagnosis, thus casting the diagnosis into doubt However, if one assumes that the discharge diagnosis of these patients was accurate, these data suggest improved outcome for those women with milder forms
of the disease [61] Samuelsson and colleagues [62] , using the Swedish Cause of Death Register, found that the case fatality rate for AFE was high and remained unaltered (42 – 48%) during the decades spanning the 1970s through 1990s Reported maternal mortality rates are summarized in Table 35.4
Neonatal outcome is similarly poor If the event occurs prior
to delivery, the neonatal survival rate is approximately 80%; only half of these fetuses survive neurologically intact [5] Fetuses sur-viving to delivery generally demonstrate profound respiratory acidemia Although at the present time no form of therapy appears to be associated with improved maternal outcome, there is a clear relationship between neonatal outcome and event - to - delivery interval in those women suffering cardiac
may, under certain circumstances and in susceptible maternal –
fetal pairs, be of immense signifi cance to the mother as well [5]
Previous experimental evidence in animals and humans
unequivocally demonstrates that the intravenous administration
of even large amounts of amniotic fl uid per se is innocuous
[21,24,60] Further, the clinical fi ndings described in the National
Registry are not consistent with an embolic event as commonly
understood (Table 35.2 ) Thus, the term “ amniotic fl uid
embo-lism ” itself appears to be a misnomer In the National Registry
analysis, the authors suggested that the term “ amniotic fl uid
embolism ” be discarded and the syndrome of acute peripartum
hypoxia, hemodynamic collapse, and coagulopathy should be
designated in a more descriptive manner, as “ anaphylactoid
syn-drome of pregnancy ”
Clinical p resentation
Clinical signs and symptoms noted in patients with AFE are
described in Table 35.2 In a typical case, a patient in labor, having
just undergone cesarean delivery or immediately following
vaginal delivery or pregnancy termination, suffers the acute onset
of profound hypoxia and hypotension followed by
cardiopulmo-nary arrest The initial episode often is complicated by the
Table 35.2 Signs and symptoms noted in patients with amniotic fl uid
embolism
Sign or symptom No of patients (%)
* Includes all live fetuses in utero at time of event
† Eighteen patients did not survive long enough for these diagnoses to be
confi rmed
‡ Eight patients did not survive long enough for this diagnosis to be confi rmed
§ One patient was intubated at the time of the event and could not be assessed
¶ Diffi cult ventilation was noted during cardiac arrest in six patients, and
wheezes were auscultated in one patient
Reproduced by permission from Clark SL, Hankins GVD, Dudley DA Amniotic
fl uid embolism: analysis of a national registry Am J Obstet Gynecol 1995; 172:
1158 – 1169
Table 35.3 Differential diagnosis of amniotic fl uid embolism
Air embolus Anaphylaxis Anesthetic toxicity Myocardial infarction Peripartum cardiomyopathy Placental abruption Pulmonary aspiration Septic shock Transfusion reaction Venous thromboembolism
Trang 3cance of histologic fi ndings in patients with pulmonary fat embolism [68]
Other putative markers for AFE, such as serum tryptase [69] , pulmonary mast cell antitryptase [70] , serum TKH - 2 antibody to fetal antigen sialyl Tn [71] , pulmonary TKH - 2 antibody to fetal antigen sialyl Tn [72] , serum complement [69] , and plasma zinc coproporphyrin I [73] , have been studied but as of yet provide
no defi nitive means of diagnosing or excluding AFE
Treatment
For the mother, the end - result of therapy remains disappointing, with a high mortality rate In the National Registry, we noted no
arrest (Table 35.5 ) [5] Similar fi ndings were reported by Katz et
al [63] in patients suffering cardiac arrest in a number of
differ-ent clinical situations
Diagnosis
In the past, histologic confi rmation of the clinical syndrome
of AFE was often sought by the detection of cellular debris of
presumed fetal origin either in the distal port of a pulmonary
artery catheter or at autopsy [32] Several studies conducted
during the past decade, however, suggest that such fi ndings
are commonly encountered, even in normal pregnant women
(Figure 35.4 ) [64 – 67] In the analysis of the National AFE
Registry, fetal elements were found in roughly 50% of cases in
which pulmonary artery catheter aspirate was analyzed and in
roughly 75% of patients who went to autopsy [5] The frequency
with which such fi ndings are encountered varies with the number
of histologic sections obtained In addition, multiple special
stains often are required to document such debris [32] Thus, the
diagnosis of AFE remains a clinical one; histologic fi ndings are
neither sensitive nor specifi c It is interesting to note that similar
conclusions have been drawn regarding the diagnostic signifi
Table 35.4 Summary of published amniotic fl uid embolism case series
Series Methodology Period AFE Incidence (1 per x births) Maternal Mortality
Gilbert 1999 [61] California population database of 1,094,248 singleton births 1994 – 1995 20,646 14/53 (26%)
Kramer 2006 [58] Canadian population based cohort of 3,018,781 deliveries 1991 – 2002 16,667 24/180 (13%) Samuelsson 2007 [62] Swedish Cause of Death Register from 2,961,000 deliveries 1973 – 1999 51,947 25/57 (44%) Abenhaim 2008 [59] U.S population based cohort study of 2,940,362 births 1998 – 2003 12,987 49/227 (22%)
* Incidence of fatal cases
* * years 1972 – 1980
Table 35.5 Cardiac arrest - to - delivery interval and neonatal outcome
Interval (min) Survival Intact survival
Reproduced by permission from Clark SL, Hankins GVD, Dudley DA Amniotic
fl uid embolism: analysis of the national registry Am J Obstet Gynecol 1995; 172:
1158 – 1169
Figure 35.4 Squamous cells recovered from the pulmonary arterial circulation
of a pregnant patient with class IV rheumatic mitral stenosis (magnifi cation,
× 1000) From Clark 1986 [66]
Trang 4to the mother and deliver the baby [5,63] For the pregnant patient, the standard ABC of cardiopulmonary resuscitation should be modifi ed to include a fourth category, D: delivery New modalities for the treatment of AFE, such as high - dose steroids [5] , extracorporeal membrane oxygenation with intra aortic balloon counterpulsation [74] , continuous hemodiafi ltra-tion [75,76] , cardiopulmonary bypass [77,78] , recombinant factor VIIa [79,80] , and nitric oxide [81] have been reported in survivors but are thus far of limited cumulative experience or demonstrated benefi t
There are limited data on risk of recurrence in a subsequent pregnancy for women who experience AFE; fewer than a dozen cases are reported in the published literature [82 – 87] At present,
it appears that the risk of recurrence is low
Despite many advances in the understanding of this condition, AFE or anaphylactoid syndrome of pregnancy remains enigmatic and in most cases is associated with dismal maternal and fetal outcomes, regardless of the quality of care rendered Thus, AFE remains unpredictable, unpreventable, and, for the most part, untreatable Further insight into this rare, but lethal, disorder may be forthcoming from the UK Obstetric Surveillance System (UKOSS), a joint initiative of the Royal College of Obstetricians and Gynaecologists and the National Perinatal Epidemiology Unit, which goal is to describe the epidemiology of a variety of uncommon disorders of pregnancy [88]
References
1 Morgan M Amniotic fl uid embolism Anaesthesia 1979 ; 34 : 29
2 Kaunitz AM , Hughes JM , Grimes DA Causes of maternal mortality
in the United States Obstet Gynecol 1985 ; 65 : 605
3 Grimes DA The morbidity and mortality of pregnancy: still a risky
business Am J Obstet Gynecol 1994 ; 170 : 1489
4 Hogberg U , Joelsson I Amniotic fl uid embolism in Sweden, 1951 –
1980 Gynecol Obstet Invest 1985 ; 20 ( 3 ): 130 – 137
5 Clark SL , Hankins GDV , Dudley DA , et al Amniotic fl uid embolism:
analysis of a national registry Am J Obstet Gynecol 1995 ; 172 : 1158
6 Meyer JR Embolia pulmonar amniocaseosa Bras/Med 1926 ; 2 :
301 – 303
7 Steiner PE , Luschbaugh CC Maternal pulmonary embolism by
amni-otic fl uid JAMA 1941 ; 117 : 1245
8 Liban E , Raz S A clinicopathologic study of fourteen cases of
amni-otic fl uid embolism Am J Clin Pathol 1969 ; 51 : 477
9 Thomson WB , Budd JW Erroneous diagnosis of amniotic fl uid
embolism Am J Obstet Gynecol 1963 ; 91 : 606
10 Resnik R , Swartz WH , Plumer MH , Benirschke K , Stratthaus ME Amniotic fl uid embolism with survival Obstet Gynecol 1976 ; 47 :
295 – 298
11 Guidotti RJ , Grimes DA , Cates W Fatal amniotic fl uid embolism
during legally induced abortion in the United States, 1972 – 1978 Am
J Obstet Gynecol 1981 ; 141 : 257
12 Cromley MG , Taylor PJ , Cummings DC Probable amniotic fl uid
embolism after fi rst trimester pregnancy termination J Reprod Med
1983 ; 28 : 209
difference in survival among patients suffering initial cardiac
arrest in small rural hospitals attended by family practitioners
compared with those suffering identical clinical signs and
symp-toms in tertiary - level centers attended by board - certifi ed
anesthe-siologists, cardiologists, and maternal – fetal medicine specialists
Nevertheless, several generalizations can be drawn
1 The initial treatment for AFE is supportive Cardiopulmonary
resuscitation is performed if the patient is suffering from a
lethal dysrhythmia Oxygen should be provided at high
concentrations
2 In the patient who survives the initial cardiopulmonary insult,
it should be remembered that left ventricular failure is commonly
seen Thus, volume expansion to optimize ventricular preload is
performed, and if the patient remains signifi cantly hypotensive,
the addition of an inotropic agent such as dopamine seems most
appropriate In patients who remain unstable following the initial
resuscitative efforts, pulmonary artery catheterization may be of
benefi t to guide hemodynamic manipulation
3 Although no evidence exists to document the benefi t of
corti-costeroids in patients with AFE, the similarities between AFE and
anaphylaxis proposed in the National Registry suggest that the
administration of high doses of corticosteroids could be a
con-sideration In the absence of any data to suggest the benefi t of
this, however, steroid treatment is not mandated by standard of
care; in fact since the original suggestion of corticosteroid therapy
by the authors of the National Registry report, we have reviewed
several cases where death resulted despite early high - dose steroid
treatment
4 In antepartum cases of AFE, careful attention must be paid to
the fetal condition In a mother who is hemodynamically unstable
but has not yet undergone cardiorespiratory arrest, maternal
con-siderations must be weighed carefully against those of the fetus
The decision to subject such an unstable mother to a major
abdominal operation (cesarean section) is a diffi cult one, and
each case must be individualized However, it is axiomatic in
these situations that where a choice must be made, maternal well
being must take precedence over that of the fetus
5 In mothers who have progressed to frank cardiac arrest, the
situation is different Under these circumstances, maternal
sur-vival is extremely unlikely, regardless of the therapy rendered In
such women, it is highly unlikely that the imposition of cesarean
section would signifi cantly alter the maternal outcome Even
properly performed cardiopulmonary resuscitation (diffi cult at
best in a pregnant woman) provides only a maximum of 30% of
normal cardiac output Under these circumstances, it is fair to
assume that the proportion of blood shunted to the uterus and
other splanchnic distributions approaches nil Thus, the fetus will
be, for practical purposes, anoxic at all times following maternal
cardiac arrest, even during ideal performance of
cardiopulmo-nary resuscitation Because the interval from maternal arrest to
delivery is directly correlated with newborn outcome,
perimor-tum cesarean delivery should be initiated immediately on the
diagnosis of maternal cardiac arrest in patients with AFE,
assum-ing suffi cient personnel are available to continue to provide care
Trang 538 Porter TF , Clark SL , Dildy GA , Hankins GDV Isolated disseminated intravascular coagulation and amniotic fl uid embolism Society of Perinatal Obstetricians 16th Annual Meeting, Poster Presentation, Kona, Hawaii, January 1996
39 Ratnoff OD , Vosburgh GJ Observations of the clotting defect in
amniotic fl uid embolism N Engl J Med 1952 ; 247 : 970
40 Beller FK , Douglas GW , Debrovner CH , et al The fi brinolytic
system in amniotic fl uid embolism Am J Obstet Gynecol 1963 ; 87 :
48
41 Courtney LD , Allington LM Effect of amniotic fl uid on blood
coagu-lation Br J Haematol 1972 ; 113 : 911
42 Phillips LL , Davidson EC Procoagulant properties of amniotic fl uid
Am J Obstet Gynecol 1972 ; 113 : 911
43 Lockwood CJ , Bach R , Guha A , et al Amniotic fl uid contains tissue
factor, a potent initiator of coagulation Am J Obstet Gynecol 1991 ;
165 : 1335
44 Parker CW In: C linical Immunology Philadelphia : WB Saunders ,
1980 : 1208
45 Smith PL , Kagey - Sobotka A , Bleecker ER , et al Physiologic
manifesta-tions of human anaphylaxis J Clin Invest 1980 ; 66 : 1072
46 Smedegard G , Revenas B , Lundberg C , Arfors KE Anaphylactic shock
in monkeys passively sensitized with human reaginic serum I
Hemodynamics and cardiac performances Acta Physiol Scand 1981 ;
111 : 239
47 Enjeti S , Bleecker ER , Smith PL , et al Hemodynamic mechanisms in
anaphylaxis Circ Shock 1983 ; 11 : 297
48 Silverman HJ , van Hook C , Haponik EF Hemodynamic changes in
human anaphylaxis Am J Med 1984 ; 77 : 341
49 Kapin MA , Ferguson JL Hemodynamic and regional circulatory
alterations in dog during anaphylactic challenge Am J Physiol 1985 ;
249 : H430
50 Lee WP , Clark SL , Cotton DB , et al Septic shock during pregnancy
Am J Obstet Gynecol 1988 ; 159 : 410
51 Raper RF , Fisher MM Profound reversible myocardial depression
after anaphylaxis Lancet 1988 ; i : 386
52 Wong S , Dykewicz MS , Patterson R Idiopathic anaphylaxis: a clinical
summary of 175 patients Arch Intern Med 1990 ; 150 : 1323
53 Parrillo JE Pathogenic mechanisms of septic shock N Engl J Med
1993 ; 328 : 1471
54 Clark SL Arachidonic acid metabolites and the pathophysiology of
amniotic fl uid embolism Semin Reprod Endocrinol 1985 ; 3 : 253
55 Paul RH , Koh BS , Bernstein SG Changes in fetal heart rate: uterine
contraction patterns associated with eclampsia Am J Obstet Gynecol
1978 ; 130 : 165
56 Towell ME Fetal acid – base physiology and intrauterine asphyxia In:
Goodwin JW , Godden JO , Chance GW , eds Perinatal Medicine
Baltimore : Williams and Wilkins , 1976 : 200
57 American College of Obstetricians and Gynecologists Prologue Amniotic fl uid embolism syndrome In: Obstetrics , 3rd edn
Gynecologists , 1993 : 94
58 Kramer MS , Rouleau J , Baskett TF , Joseph KS , Maternal Health Study Group of the Canadian Perinatal Surveillance System Amniotic - fl uid embolism and medical induction of labour: a retrospective
popula-tion - based cohort study Lancet 2006 ; 368 : 1444 – 1448
59 Abenhaim HA , Azoulay L , Kramer MS , et al Incidence and risk factors of amniotic fl uid embolisms: a population - based study
on 3 million births in the United States Am J Obstet Gynecol 2008 ;
199 ( 1 ): 49
13 Meier PR , Bowes WA Amniotic fl uid embolus - like syndrome
pre-senting in the second trimester of pregnancy Obstet Gynecol 1983 ;
61 (suppl): 31
14 Eastman NJ Editorial comment Obstet Gynecol Surv 1948 ; 3 : 35
15 Cron RS , Kilkenny GS , Wirthwein C , et al Amniotic fl uid embolism
Am J Obstet Gynecol 1952 ; 64 : 1360
16 Schneider CL Coagulation defects in obstetric shock: meconium
embolism and defi brination Am J Obstet Gynecol 1955 ; 69 : 748
17 Jacques WE , Hampton JW , Bird RM , et al Pulmonary hypertension
and plasma thromboplastin antecedent defi ciency in dogs Arch
Pathol 1960 ; 69 : 248
18 Halmagyi DFJ , Starzecki B , Shearman RP Experimental amniotic
fl uid embolism: mechanism and treatment Am J Obstet Gynecol 1962 ;
84 : 251
19 Attwood HD , Downing SE Experimental amniotic fl uid embolism
Surg Gynecol Obstet 1965 ; 120 : 255
20 Reis RL , Pierce WS , Behrendt DM Hemodynamic effects of amniotic
fl uid embolism Surg Gynecol Obstet 1969 ; 129 : 45
21 Stolte L , van Kessel H , Seelen J , et al Failure to produce the syndrome
of amniotic fl uid embolism by infusion of amniotic fl uid and
meco-nium into monkeys Am J Obstet Gynecol 1967 ; 98 : 694
22 MacMillan D Experimental amniotic fl uid embolism J Obstet
Gynaecol Br Comwlth 1968 ; 75 : 8
23 Dutta D , Bhargava KC , Chakravarti RN , et al Therapeutic studies in
experimental amniotic fl uid embolism in rabbits Am J Obstet Gynecol
1970 ; 106 : 1201
24 Adamsons K , Mueller - Heubach E , Myer RE The innocuousness of
amniotic fl uid infusion in the pregnant rhesus monkey Am J Obstet
Gynecol 1971 ; 109 : 977
25 Kitzmiller JL , Lucas WE Studies on a model of amniotic fl uid
embo-lism Obstet Gynecol 1972 ; 39 : 626
26 Reeves JT , Daoud FS , Estridge M , et al Pulmonary pressor effects of
small amounts of bovine amniotic fl uid Respir Physiol 1974 ; 20 : 231
27 Spence MR , Mason KG Experimental amniotic fl uid embolism in
rabbits Am J Obstet Gynecol 1974 ; 119 : 1073
28 Azegami M , Mori N Amniotic fl uid embolism and leukotrienes Am
J Obstet Gynecol 1986 ; 155 : 1119
29 Richards DS , Carter LS , Corke B , et al The effect of human amniotic
fl uid on the isolated perfused rat heart Am J Obstet Gynecol 1988 ;
158 : 210
30 Hankins GDV , Snyder RR , Clark SL , et al Acute hemodynamic and
respiratory effects of amniotic fl uid embolism in the pregnant goat
model Am J Obstet Gynecol 1993 ; 168 : 1113
31 Petroianu GA , Altmannsberger SH , Maleck WH , et al Meconium and
amniotic fl uid embolism: effects on coagulation in pregnant mini
pigs Crit Care Med 1999 ; 27 : 348
32 Clark SL New concepts of amniotic fl uid embolism: a review Obstet
Gynecol Surv 1990 ; 45 : 360
33 Clark SL , Montz FJ , Phelan JP Hemodynamic alterations in amniotic
fl uid embolism: a reappraisal Am J Obstet Gynecol 1985 ; 151 : 617
34 Clark SL , Cotton DB , Gonik B , et al Central hemodynamic
altera-tions in amniotic fl uid embolism Am J Obstet Gynecol 1988 ; 158 :
1124
35 Girard P , Mal H , Laine JR , et al Left heart failure in amniotic fl uid
embolism Anesthesiology 1986 ; 64 : 262
36 Courtney LD Coagulation failure in pregnancy BMJ 1970 ; 1 : 691
37 Shechtman M , Ziser A , Markovits R , Rozenberg B Amniotic fl uid
embolism: early fi ndings of transesophageal echocardiography
Anesth Analg 1999 ; 89 : 1456
Trang 676 Kaneko Y , Ogihara T , Tajima H , Mochimaru F Continuous hemo-diafi ltration for disseminated intravascular coagulation and shock
due to amniotic fl uid embolism: report of a dramatic response Intern Med 2001 ; 40 : 945 – 947
77 Esposito RA , Grossi EA , Coppa G , et al Successful treatment of post-partum shock caused by amniotic fl uid embolism with cardiopulmo-nary bypass and pulmocardiopulmo-nary artery thromboembolectomy Am J Obstet Gynecol 1990 ; 163 : 572 – 574
78 Stanten RD , Iverson LI , Daugharty TM , Lovett SM , Terry C , Blumenstock E Amniotic fl uid embolism causing catastrophic pul-monary vasoconstriction: diagnosis by transesophageal
echocardio-gram and treatment by cardiopulmonary bypass Obstet Gynecol 2003 ;
102 : 496 – 498
79 Lim Y , Loo CC , Chia V , Fun W Recombinant factor VIIa after amni-otic fl uid embolism and disseminated intravascular coagulopathy
Int J Gynaecol Obstet 2004 ; 87 : 178 – 179
80 Prosper SC , Goudge CS , Lupo VR Recombinant factor VIIa to suc-cessfully manage disseminated intravascular coagulation from
amni-otic fl uid embolism Obstet Gynecol 2007 ; 109 : 524 – 525
81 McDonnell NJ , Chan BO , Frengley RW Rapid reversal of critical haemodynamic compromise with nitric oxide in a parturient with
amniotic fl uid embolism Int J Obstet Anesth 2007 ; 16 : 269 – 273
82 Clark SL Successful pregnancy outcomes after amniotic fl uid
embo-lism Am J Obstet Gynecol 1992 ; 167 : 511
83 Duffy BL Does amniotic fl uid embolism recur ? Anaesth Intens Care
1998 ; 26 : 333
84 Collier C Recurring amniotic fl uid embolism Anaesth Intens Care
1998 ; 26 : 599 – 600
85 Stiller RJ , Siddiqui D , Laifer SA , Tiakowski RL , Whetham JC Successful pregnancy after suspected anaphylactoid syndrome of
pregnancy (amniotic fl uid embolus) A case report J Reprod Med
2000 ; 45 : 1007
86 Demianczuk CE , Corbett TF Successful pregnancy after amniotic
fl uid embolism: a case report J Obstet Gynaecol Can 2005 ; 27 :
699 – 701
87 Abecassis P , Benhamou D Is amniotic fl uid embolism likely to recur
in a subsequent pregnancy? Int J Obstet Anesth 2006 ; 15 : 90
88 Knight M , Kurinczuk JJ , Tuffnell D , Brocklehurst P The UK Obstetric Surveillance System for rare disorders of pregnancy Br J Obstet Gynaecol 2005 ; 112 : 263 – 265
89 Tuffnell DJ , Johnson H Amniotic fl uid embolism: the UK register
Hosp Med 2000 ; 61 : 532 – 534
90 Burrows A , Khoo SK The amniotic fl uid embolism syndrome: 10
years ’ experience at a major teaching hospital Aust N Z J Obstet Gynaecol 1995 ; 35 ( 3 ): 245 – 50
60 Sparr RA , Pritchard JA Studies to detect the escape of amniotic fl uid
into the maternal circulation during parturition Surg Gynecol Obstet
1958 ; 107 : 550
61 Gilbert WM , Danielsen B Amniotic fl uid embolism: decreased
mor-tality in a population - based study Obstet Gynecol 1999 ; 93 : 973
62 Samuelsson E , Hellgren M , H ö gberg U Pregnancy - related deaths due
to pulmonary embolism in Sweden Acta Obstet Gynecol Scand 2007 ;
86 : 435 – 443
63 Katz VJ , Dotters DJ , Droegemueller W Perimortem cesarean
delivery O bstet Gynecol 1986 ; 68 : 571
64 Plauche WC Amniotic fl uid embolism Am J Obstet Gynecol 1983 ;
147 : 982
65 Covone AE , Johnson PM , Mutton D , et al Trophoblast cells in
peripheral blood from pregnant women Lancet 1984 ; i : 841
66 Clark SL , Pavlova Z , Horenstein J , et al Squamous cells in the
mater-nal pulmonary circulation Am J Obstet Gynecol 1986 ; 154 : 104
67 Lee W , Ginsburg KA , Cotton DB , Kaufman RH Squamous and
tro-phoblastic cells in the maternal pulmonary circulation identifi ed by
invasive hemodynamic monitoring during the peripartum period
Am J Obstet Gynecol 1986 ; 155 : 999
68 Gitin TA , Seidel T , Cera PJ , et al Pulmonary microvascular fat: the
signifi cance? Crit Care Med 1993 ; 21 : 664
69 Benson MD , Kobayashi H , Silver RK , Oi H , Greenberger PA , Terao
T Immunologic studies in presumed amniotic fl uid embolism Obstet
Gynecol 2001 ; 97 : 510 – 514
70 Fineschi V , Gambassi R , Gherardi M , Turillazzi E The diagnosis of
amniotic fl uid embolism: an immunohistochemical study for the
quantifi cation of pulmonary mast cell tryptase Int J Legal Med 1998 ;
111 : 238 – 243
71 Ohi H , Kobayashi H , Sugimura M , Terao T [A new method for
diagnosis of amniotic fl uid embolism by means of monoclonal
anti-body TKH - 2 that recognizes mucin - type glycoprotein, a component
in meconium.] Nippon Sanka Fujinka Gakkai Zasshi 1992 ; 44 :
813 – 819
72 Oi H , Kobayashi H , Hirashima Y , Yamazaki T , Kobayashi T , Terao
T Serological and immunohistochemical diagnosis of amniotic fl uid
embolism Semin Thromb Hemost 1998 ; 24 : 479 – 484
73 Kanayama N , Yamazaki T , Naruse H , Sumimoto K , Horiuchi K ,
Terao T Determining zinc coproporphyrin in maternal plasma – a
new method for diagnosing amniotic fl uid embolism Clin Chem
1992 ; 38 : 526 – 529
74 Hsieh YY , Chang CC , Li PC , Tsai HD , Tsai CH Successful application
of extracorporeal membrane oxygenation and intra - aortic balloon
counterpulsation as lifesaving therapy for a patient with amniotic
fl uid embolism Am J Obstet Gynecol 2000 ; 183 : 496 – 497
75 Weksler N , Ovadia L , Stav A , Ribac L , Iuchtman M Continuous
arteriovenous hemofi ltration in the treatment of amniotic fl uid
embolism Int J Obstet Anesth 1994 ; 3 : 92 – 96
Trang 7Critical Care Obstetrics, 5th edition Edited by M Belfort, G Saade,
M Foley, J Phelan and G Dildy © 2010 Blackwell Publishing Ltd.
Antiphospholipid Syndrome
T Flint Porter 1 & D Ware Branch 2
1 Department of Obstetrics and Gynecology, University of Utah Health Science UT and Maternal - Fetal Medicine, Urban Central
Region, Intermountain Healthcare, Salt Lake City, UT, USA
2 Department of Obstetrics and Gynecology, University of Utah Health Sciences Center and Women and Newborns Services,
Intermountain Healthcare, Salt Lake City, UT, USA
Introduction
Systemic lupus erythematosus (SLE) is a chronic infl ammatory
condition that affects virtually every organ system With an
increased prevalence among women of reproductive age, it is the
autoimmune disease most commonly encountered during
preg-nancy The majority of women with stable, uncomplicated SLE
tolerate pregnancy well with relatively few serious obstetric
com-plications However, women with poorly controlled disease and/
or serious SLE - related end - organ disease are at substantial risk
for maternal morbidity and even mortality, as well as several
adverse obstetric outcomes Antiphospholipid syndrome (APS)
is another autoimmune condition associated with several adverse
pregnancy outcomes Anticoagulation prophylaxis reduces the
risk of thromboembolism and fetal death but the incidence of
pre - eclampsia, uteroplacental insuffi ciency, and preterm birth
remain high
Management of both SLE and APS during pregnancy requires
vigilance for signs and symptoms of disease exacerbation,
aggres-sive immunosuppresaggres-sive treatment when needed, and careful
assessment of fetal well - being A multidisciplinary approach is
essential and should include the rheumatologist, obstetrician, and
if renal disease is present, the patient ’ s nephrologist
Systemic l upus e rythematosus in p regnancy
Background
The prevalence of SLE varies depending on the population under
study but generally ranges between 5 and 125 per 100 000 and
affects women 5 – 10 times more often than men [1,2] The peak
age of onset in young women occurs between their late teens and
early 40s [3] The prevalence among ethnic groups, such as those
with African or Asian ancestry, is highest and the disease appears
to be more severe when compared to white patients Familial studies indicate that genetic susceptibility to lupus involves several complex gene polymorphisms Russell and colleagues [4] reported a linkage between susceptibility to lupus in family members and disequilibrium in polymorphisms located on the long arm of chromosome 1, 1q23 – 24 Genes coding for C - reactive protein (CRP), actively involved in apoptosis, have been mapped
to this area and CRP levels are commonly low in patients with lupus Another familial study suggested that a single nucleotide
polymorphism within the programmed cell death 1 gene ( PDCD1 )
is associated with the development of the disease in both European and Mexican populations [5]
SLE e xacerbation ( fl are) d uring p regnancy
Based on published reports, fl are occurs in about 30 – 60% of pregnant patients with lupus Renal disease and disease activity appear to increase the rate of fl are during pregnancy There is a split of opinion about whether pregnancy itself predisposes to lupus fl are [2] All studies are hampered by the fact that many of the most common signs and symptoms of lupus fl are also occur
in normal pregnancy Some studies show higher rates of fl are in pregnant women compared to non - pregnant controls, even when disease is inactive at the time of conception [6 – 11] Others report
no difference in rates of fl are in women with well - controlled disease, whether treated or untreated, and non - pregnant women [12 – 18] Importantly, in nearly all studies, fl ares during preg-nancy are reported to be mild to moderate in nature and easily treated with glucocorticoids
Women with pre - existing renal disease, even when inactive, are undoubtedly at greatest risk for SLE fl are during pregnancy [3,9] Pregnancy may predispose to deterioration of renal function, especially for women with active lupus nephritis (LN) and/or renal insuffi ciency before conception [19 – 21] Tandon and col-leagues [22] reported that LN patients with inactive renal disease showed changes in disease activity and deterioration in renal function during pregnancy that were similar to those in non pregnant patients with active LN Overall, about one - third of
Trang 8[21] and in 40% with pre - existing proteinuria as defi ned by
> 300 mg/24 h or a creatinine clearance < 100 mL/min [30] Not surprisingly, the most important risk factor for pregnancy loss in women with SLE is coexisting APS In one series of preg-nant women with SLE, the presence of antiphospholipid antibod-ies had a positive predictive value for pregnancy loss of 50% [40]
In another, positive predictive value increased to over 85% if women with SLE also had a fetal death in a prior pregnancy [32]
Neonatal l upus e rythematosus
Neonatal lupus erythematosus (NLE) is a rare condition of the fetus and neonate, occurring in 1 of 20 000 of all live births and
in fewer than 5% of all women with SLE [41] Dermatological NLE is most common and is described as erythematous, scaling annular or elliptical plaques occurring on the face or scalp, analo-gous to the subacute cutaneous lesions in adults Lesions appear
in the fi rst weeks of life, probably induced by exposure of the skin
to ultraviolet light, and may last for up to 6 months [42] Hypopigmentation may persist for up to 2 years A small percent-age of affected infants will go on to have other autoimmune diseases later in life [42] Hematological NLE is rare and may be manifest as autoimmune hemolytic anemia, leukopenia, throm-bocytopenia and hepatosplenomegaly
Cardiac NLE lesions include congenital complete heart block (CCHB) and the less frequently reported endocardial fi broelas-tosis Endomyocardial fi brosis caused by NLE leads to interrup-tion of the conducinterrup-tion system, especially in the area of the atrioventricular node The diagnosis is typically made around 23 weeks of gestation [43] when a fi xed bradycardia, in the range of
60 – 80 beats/min, is detected during a routine prenatal visit Fetal echocardiography reveals complete atrioventricular dissociation with a structurally normal heart The prognosis varies but in the
most severe cases, hydrops fetalis develops in utero Because the
endomyocardial damage is permanent, a pacemaker may be nec-essary for neonatal survival In the largest series of 113 cases diagnosed before birth, 19% died, of which 73% died within 3 months of delivery [43] In that same series, the 3 - year survival was 79% Cutaneous manifestations of NLE have also been reported in infants with CCHB [42]
Not all women who give birth to babies with NLE have been previously diagnosed with an autoimmune disorder [42,44] However, in one study, 7 of 13 previously asymptomatic mothers who delivered infants with dermatologic NLE were later diagnosed with one of several autoimmune disorders [42] Surprisingly, asymptomatic women who deliver infants with CCHB are less likely to later develop an autoimmune disorder than those with dermatologic manifestations alone [44] Fetal immunologic damage is probably caused by maternal autoantibodies that cross the placenta and bind to fetal tissue [45 – 49] Anti - Ro/SSA antibodies are found in 75 – 95% mothers who deliver babies with NLE [43,45,50] A smaller percentage have anti - La/SSB, and some have both [50] Dermatological NLE has also been associated with anti - U1RNP without anti - Ro/SSA
or anti - La/SSB [50,51] Of mothers with SLE who are
serologi-women with renal disease experience fl are during pregnancy,
fewer than 25% have worsening renal function, and only 10% of
have permanent deterioration Renal deterioration appears to be
less severe in women with inactive LN in the 6 months before
conception [9,14,19,21,23,24]
Pulmonary hypertension arises in up to 14% of patients with
lupus, and even mildly raised pulmonary artery pressures can be
seen in 37% of patients [25] Though fortunately rare during
pregnancy, pulmonary hypertension confers an unacceptably
high risk of maternal death and patients should be counseled
accordingly
Obstetric c omplications in w omen with SLE
Women with SLE are at risk for several obstetric complications,
sometimes resulting in serious maternal and perinatal
morbid-ity Between 20 and 30% of women with SLE have pregnancies
complicated by pre - eclampsia [10,21,26] Uteroplacental
insuf-fi ciency resulting in intrauterine growth restriction (IUGR) or
small for gestational age neonates occurs in 12 – 40% of lupus
pregnancies [6,9,12,26,27] The risk of IUGR is highest for
women with renal insuffi ciency and/or hypertension [28,29]
Preterm birth is also more common in pregnancies complicated
by SLE [7 – 10,12,26] Most of preterm deliveries in women with
SLE probably occur iatrogenically because of disease
exacerba-tion and/or obstetric complicaexacerba-tions, though a higher risk of
preterm premature rupture of membranes has been reported
The likelihood of serious obstetric complications is highest for
women with poorly controlled disease, renal disease and/or
chronic hypertension, and APS [10,21,27,28,31,32] Chronic
steroid use may also contribute to higher rates of pre - eclampsia
and IUGR
Pregnancy loss is thought to be more prevalent among women
with SLE, with rates ranging from 10 to 50% [11,16,17,29,33]
First - trimester loss occurs in about 20% of lupus pregnancies, not
markedly higher than the general population [34] However,
still-birth (after 20 weeks of gestation) rates are elevated in several
studies [9,14,21,35,36] In one series, 20% of losses occurred
during the second or third trimester [35] Disease activity
increases the likelihood of pregnancy loss [9,14] with one study
reporting live births in 64% of women with active disease within
6 months of conception, compared to 88% in women with
qui-escent disease [21] In the Hopkins Lupus Pregnancy Cohort,
increased lupus activity did not increase the risk for miscarriage,
but the stillbirth rate was threefold higher [36] The timing of
lupus activity affects the pregnancy loss rate, with activity early
in pregnancy being the most dangerous Proteinuria,
thrombo-cytopenia, and hypertension in the fi rst trimester are each
inde-pendent risk factors for pregnancy loss Women with these risk
factors have a 30 – 40% chance of suffering a pregnancy loss [37]
Accordingly, pregnancy loss is more likely if SLE is diagnosed
during the index pregnancy [38,39]
Renal insuffi ciency is also important; one group reported fetal
loss in 50% of pregnancies complicated by moderate to severe
renal insuffi ciency as defi ned by serum creatinine > 1.5 mg/dL
Trang 9cally positive for anti - Ro/SSA antibodies, 15% will have infants
affected with dermatological SLE; the proportion who deliver
infants with CCHB is much smaller However, once a woman
with SLE and anti - Ro/SSA antibodies delivers one infant with
CCHB, her risk for recurrence is at least two - to threefold higher
than other women with anti - SSA/Ro - SSB/La antibodies who have
never had an affected child [45]
There is no known in utero therapy that completely reverses
fetal CCHB secondary to SLE However, there is some evidence
that treatment with glucocorticoids, plasmapheresis, intravenous
immune globulin or some combination thereof, may slow the
progression of prenatally diagnosed CCHB or at least prevent
recurrence in a future pregnancy [52] In utero treatment with
dexamethasone was felt to slow disease progression in one case
report of hydrops secondary to CCHB [53] In one retrospective
study, maternally administered dexamethasone appeared to
prevent progression from second - degree block to third - degree
block [54] In a large series of 87 pregnancies at risk for NLE,
mothers who received corticosteroids before 16 weeks of
gesta-tion were less likely to deliver infants with CCHB compared to
mothers who received no therapy [55] However, there was no
benefi t to treatment when CCHB was diagnosed in utero In utero
treatment with digoxin is not benefi cial for prenatally diagnosed
CCHB [56]
Diagnosis of SLE and d etection of SLE
e xacerbation ( fl are)
Thorough and frequent clinical assessment remains essential for
the timely and accurate detection of SLE fl are [2] In pregnancy,
detection is more diffi cult because many of the typical signs and
symptoms associated with fl are are considered normal (Table
36.1 ) The SLE disease activity index (SLEDAI) has been modifi ed
Table 36.1 Common symptoms in pregnancy that may mimic lupus fl are
Constitutional • Debilitating fatigue; may worsen throughout
pregnancy
Skin • Palmar erythema
• Facial blush due to increased estrogen levels
Face • Melasma; photosensitive rash over cheeks and
forehead
Hair • Increased hair thickness and growth
• Hair loss postpartum
Pulmonary • Increased respiratory rate secondary to
increased progesterone levels
• Dyspnea
Musculoskeletal • Back pain
䊊 Relaxin loosens sacroiliac joint and pubis
䊊 Gravid uterus increases lumbar lordosis
• Joint effusions
Central Nervous System • Headache, normal in pregnancy as well as in
preeclampsia
Table 36.2 Preeclampsia versus Lupus Flare
Preeclampsia SLE Flare
• Gestational age After 20 weeks ’ Anytime
• Complement (C3 & C4) Normal Usually low
• Anti - DS DNA antibodies Negative Usually positive
for pregnancy with several caveats to rule out normal pregnancy complications and thereby more accurately identify true SLE activity [2,43] ) The most common presenting symptom in both
fl are and new onset disease is extreme fatigue Fever, weight loss, myalgia and arthralgia are also very common [57] In pregnancy, skin rashes are more frequent than musculoskeletal manifesta-tions [8] Patients with LN exhibit worsening proteinuria along with pyuria, hematuria and urinary casts Not surprisingly, SLE fl are in pregnant women with LN is easily confused with the development of pre - eclampsia/eclampsia syndromes (Table 36.2 )
Serological evaluation of SLE disease activity may be benefi cial
in confi rming fl are in confusing cases However, no study has found serial laboratory testing superior to thorough clinical assessment and if fl are is suspected, treatment should not be reserved only for women with positive serologic evaluation Even
so, the most specifi c serologic sign of SLE fl are is an elevation in anti - double - stranded DNA (anti - ds DNA) which precedes lupus
fl are in more than 80% of patients [58 – 60] In pregnancy, ele-vated anti - ds DNA titers have also been shown to correlate with the need for preterm delivery [61] and in combination with aCL antibodies, with an increased risk of fetal loss
Serial evaluation of complement levels has been suggested as method of predicting SLE fl are during pregnancy Devoe [62] reported that SLE fl are was signaled by a decline of C3 and C4 into the subnormal range and Buyon [63] reported that the phys-iologic rise in C3 and C4 levels normally seen during pregnancy did not occur in women with active disease The same group reported that activation of the alternative complement pathway
Trang 10chronic glucocorticoid therapy are the same as in non - pregnant patients and include weight gain, striae, acne, hirsutism, immu-nosuppression, osteonecrosis and gastrointestinal ulceration During pregnancy, chronic glucocorticoid therapy has also been associated with an increased risk of pre - eclampsia [35,73 – 75] , uteroplacental insuffi ciency [75] , and glucose intolerance [73,74] Women chronically treated with glucocorticoids should be screened for gestational diabetes at 22 – 24, 28 – 30 and 32 – 34 weeks of gestation
Hydroxychloroquine
Hydroxychloroquine (HCQ) has been proven to decrease the risk
of SLE fl are, improve the prognosis of SLE nephritis, and prevent death [76 – 79] It also has the lowest side - effect profi le of any medication available to treat SLE and is well tolerated by most patients In the past, many patients and their physicians discon-tinued hydroxychloroquine in pregnancy because of concerns about teratogenicity including ototoxicity [80] and eye damage [81] However, an accumulating body of evidence suggests that hydroxychloroquine can be used safely for the treatment of SLE during pregnancy [82 – 86] and is in fact superior to glucocorti-coids for women who require maintenance therapy during preg-nancy [87] An expert panel of international physicians have recommended the continuation of HCQ during pregnancy [79]
Immunosuppressants
Azathioprine (Imuran) is probably the safest immunosuppres-sant medication taken during pregnancy The fetal liver does not have the enzyme required to metabolize azathioprine into its active form [79] Series of pregnancies exposed to azathioprine for infl ammatory bowel disease or renal transplants show no signifi cant increase in fetal abnormalities among renal transplant patients Nearly 40% of the offspring were small for gestational age But this may also have been due to the underlying illness and/
or contemporaneous treatment with glucocorticoids [78,79] Most authorities recommend continuation of azathioprine treat-ment during pregnancy [57] Cyclophosphamide is reportedly teratogenic in both animal [88] and human studies [89,90] and should be avoided during the fi rst trimester Thereafter, cyclo-phosphamide should be used only in unusual circumstances such
as in women with severe, progressive proliferative glomerulone-phritis [1] Methotrexate is well known to kill chorionic villi and cause fetal death and its use should be scrupulously avoided
NSAID p reparations
The most common types of analgesics used in the treatment of SLE are non - steroidal anti - infl ammatory drugs (NSAIDs) Unfortunately, their use in pregnancy should be avoided after the
fi rst trimester because they readily cross the placenta and block prostaglandin synthesis in a wide variety of fetal tissues Though short - term tocolytic therapy with indomethacin appears to be safe [91,92] , chronic use has been associated with a number of untoward fetal effects and, when used after 32 weeks, may result
in constriction or closure of the fetal ductus arteriosus [93]
accompanies fl are during pregnancy [63] and that a combination
of low C3, C4, or CH50 levels accompanied by an elevation in
complement split products is useful in detecting fl are during
pregnancy [63] The results of other studies of complement
acti-vation in pregnant women with SLE have either been inconsistent
or not predictive of SLE fl are [11,64,65] Lockshin [66] reported
normal concentrations of the Cls – C1 inhibitor complex in
preg-nant patients with hypocomplementemia which suggests poor
synthesis of complement components rather than excessive
consumption
Laboratory confi rmation of SLE fl are is probably most helpful
in women with active LN in whom proteinuria, hypertension and
evidence of multiorgan dysfunction may easily be confused with
pre - eclampsia Both elevated anti - ds DNA titers and urinary
sedi-ment with cellular casts and hematuria weigh in weigh in favor
of active LN An increase in proteinuria in women with pre
existing LN should not necessarily raise an alarm until it doubles
[57] Pre - eclampsia is more likely in women with decreased levels
of antithrombin - III [67,68] Complement concentrations are not
helpful because activation may also occur in women with pre
eclampsia [69] In the most severe and confusing cases, the
diag-nosis can be confi rmed only with renal biopsy However, in
reality, concerns about maternal and fetal well - being often
prompt delivery, rendering the distinction between the SLE fl are
and pre - eclampsia clinically moot
Medications u sed for SLE d uring p regnancy
Glucocorticoids
The group of drugs most commonly given to pregnant women
with SLE is the glucocorticoid preparations, both as maintenance
therapy and in “ bursts ” to treat suspected SLE fl ares The doses
used in pregnancy are the same as those in non - pregnant patients
Pregnancy per se is not an indication to reduce the dose of
glu-cocorticoids, though a carefully monitored reduction in dosage
may be reasonable in appropriately selected women whose disease
appears to be in remission Some groups have recommended
prophylactic glucocorticoid therapy during pregnancy [17,24,70]
but no controlled studies have shown this practice to be prudent
or necessary in women with inactive SLE Moreover, good
mater-nal and fetal outcomes are achieved without prophylactic
treat-ment of women with stable disease [13] In contrast, glucocorticoid
treatment of women with active disease and/or elevated anti - ds
DNA titers has been shown to result in fewer relapses and better
pregnancy outcomes [14,58]
While glucocorticoids have a low potential for teratogenesis
[71] , they are not without risk during pregnancy Patients
requir-ing chronic maintenance therapy are best treated with
predniso-lone or methylprednisopredniso-lone because of their conversion to
relatively inactive forms by the abundance of 11 - ,B - ol
dehydro-genase found in the human placenta Glucocorticoids with fl
uo-rine at the 9a position (dexamethasone, betamethasone) are
considerably less well metabolized by the placenta and chronic
use during pregnancy should be avoided Both have been
associ-ated with untoward fetal effects [72] Maternal side effects of