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Severe preeclampsia, including the HELLP (hemolysis,

elevated liver enzymes, and low platelet count) syn-

drome, has been shown to increase maternal and neona-

tal morbidity and mortality rates,1 particularly if occur-

ring in the second trimester.2, 3 The usual management of

severe preeclampsia remote from term has been the de-

livery of the fetus, regardless of gestational age.1 Recently,

expectant management of women with severe pre-

eclampsia but without the HELLP syndrome between 28

and 32 weeks gestation has been shown to reduce neona-

tal complications and neonatal stay in the intensive care

unit.4

In the second trimester, expectant managementwith aggressive monitoring of the status of both mother

and fetus improves perinatal outcomes.5 The success of

this management, however, is limited by adverse maternal

outcomes occurring in women with severe preeclampsia

at the mid trimester.2

An increased risk of maternal morbidity and death is

reported in women with the HELLP syndrome, particu-

larly in those with a platelet count


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In addition, women with the HELLP syndrome were re-

ported to have an increased risk of adverse maternal out-

come in comparison with those who had severe pre-

eclampsia but not the HELLP syndrome.7, 8 However, the

differences in the outcomes observed in these studies

may be related to earlier gestation in women with the

HELLP syndrome than in women with severe preeclamp-

sia alone and may also reflect a greater severity of the dis-

ease process. To clarify this hypothesis, we conducted thisstudy to determine whether onset of the HELLP syn-

drome at 28.0 weeks gestation is associated with an in-

creased risk of maternal and perinatal morbidity in com-

parison with the risk associated with severe preeclampsia

without the HELLP syndrome at a similar gestational age.

Material and methods

We reviewed the medical records of women with the

HELLP syndrome and of those with severe preeclampsia

but without the HELLP syndrome who were admitted to

the E.H. Crump Womens Hospital, Memphis, Tennessee

(between July 1, 1992, and April 30, 1999) and to the

Central Baptist Hospital, Lexington, Kentucky (betweenMarch 1, 1994, and April 30, 1999). Women with a history

of hematologic or liver diseases were excluded from

analysis.

The HELLP syndrome was defined by using the strict

criteria of Sibai9 to avoid any misinterpretation of the re-

sults regarding different diagnostic criteria for the

HELLP syndrome or incomplete HELLP syndrome. The

diagnosis was made by the presence of all 3 of the follow-

ing criteria: hemolysis (characteristic peripheral blood

smear and serum lactate dehydrogenase >600 U/L or

serum total bilirubin 1.2 mg/dL), elevated liver en-

zymes (serum aspartate aminotransferase 70 U/L), and

low platelet counts (160 mm Hg or diastolic blood pressure

>110 mm Hg, headache, visual disturbances, epigastric or

right-upper-quadrant pain, eclampsia, pulmonary edema,

and proteinuria (urinary protein level >5 g/24 h). Women

with severe preeclampsia selected for analysis also met allthe following laboratory criteria: platelet count 150,000

cells/L, serum lactate dehydrogenase


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3%; odds ratio, 10.3; 95% confidence interval, 1.2-88.4;

P < .05). No statistical differences were found between

the 2 groups for all other adverse maternal outcomes

studied.

The perinatal mortality rate for both groups was 250 of

1000 women. The stillbirth rates for women with the

HELLP syndrome and for those without the HELLP cri-

teria were statistically similar (16% vs 9%; odds ratio, 1.8;

confidence interval, 0.4-8.3; P= .70). Neonatal mortality

and morbidity rates are presented in Table IV. No statisti-

cal differences were found in the neonatal outcomes be-

tween the 2 groups.

Volume 183, Number 6 Haddad et al 1477Am J Obstet Gynecol

Table I. Clinical findings in 2 study groups

HELLP syndrome (n = 32) Preeclampsia without HELLP syndrome (n = 32)

Age (y, mean SD)* 24.4 4.7 21.9 4.7Gestational age at diagnosis (wk, mean SD) 25.8 2.5 26.2 1.5Arterial blood pressure (mm Hg, mean SD) 130 18 132 11Maternal stay (d, mean SD) 7.8 2.7 9.5 8.1African-American (No.) 19 (59%) 24 (75%)Nulliparity (No.) 16 (50%) 18 (56%)Previous preeclampsia (No.) 14 (44%) 18 (56%)Chronic hypertension (No.) 4 (13%) 10 (31%)Headache (No.) 9 (28%) 14 (44%)Visual change (No.) 6 (19%) 6 (19%)Nausea and vomiting (No.) 13 (41%) 2 (6%)Epigastric or right-upper-quadrant pain (No.) 19 (59%) 3 (9%)Corticosteroid prophylaxis (No.) 18 (67%) 24 (83%)ll

*P< .05.P< .01.P< .0001.Five stillbirths excluded from analysis.llThree stillbirths excluded from analysis.

Table II. Laboratory findings in 2 study groups

HELLP syndrome (n = 32) Preeclampsia without HELLP syndrome (n = 32)

Platelet count nadir (103/L)* 57 (17-95) 195 (153-292)Lactate dehydrogenase (U/L)* 1347 (407-5720) 228 (152-431)Aspartate aminotransferase (U/L)* 182 (71-2924) 29 (12-56)Serum creatinine (mg/dL) 0.9 (0.5-10.4) 0.9 (0.6-5.3)Serum uric acid (mg/dL) 7.3 (2.8-20) 7 (4.5-12.3)

Values are expressed as median and range.*P< .001.

Table III. Maternal complications in 2 study groups

HELLP syndrome Preeclampsia without(n = 32) HELLP (n = 32)

No. % No. % Odds ratio and 95% confidence interval

Eclampsia 5 16 4 13 1.3 (0.3-5.3)Abruptio placentae 2 6 3 9 0.6 (0.1-4.1)DIC 4 13 0 NA Transfusion of blood products* 8 25 1 3 10.3 (1.2-88.4)Acute renal failure 1 3 0 NAAscites 2 6 5 16 0.4 (0.1-2)Pulmonary edema 4 13 2 6 2.1 (0.4-12.6)Pleural effusion 1 3 1 3 1Cesarean delivery 25 93 29 100 NACesarean delivery for fetal distress 4 16 8 28 0.5 (0.1-1.9)

NA, Not applicable.*P< .05.Five stillbirths excluded from analysis.

Three stillbirths excluded from analysis.


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Comment

The ultimate goal of any protocol for management of

severe preeclampsia is to reduce maternal mortality and

morbidity rates, followed by delivery of a healthy and ma-

ture baby. Seven percent of the cases of severe pre-

eclampsia occur in the second trimester, and the gesta-tional age has a critical influence on perinatal outcome.2

The optimal management in the second trimester usually

depends on balancing the risks to the mother and fetus

resulting from expectant management against the risks of

extreme prematurity in the event of immediate delivery.3

Severe preeclampsia occurring in the second trimester

has been reported to be associated with an increased in-

cidence of adverse maternal outcomes, with a high rate of

abruptio placentae (22%), HELLP syndrome (17%),

eclampsia (17%), and DIC (8%).2 Under these adverse

maternal conditions, expeditious delivery has been rec-

ommended because the risks resulting from a delayed de-

livery outweigh the possible benefits of pregnancy pro-

longation.10

The overall rate of adverse maternal outcomes ob-

served in women with the HELLP syndrome (44%) was

similar to that observed in those with severe preeclampsia

but not the HELLP syndrome (38%) during the second

trimester. Except for hematologic changes, the inci-

dences of all other adverse maternal outcomes studied

among women with the HELLP syndrome and those with

severe preeclampsia but not the HELLP syndrome were

not statistically different. Our finding of similar rates of

eclampsia in women with the HELLP syndrome and in

those with severe preeclampsia only is not in agreementwith that of Martin et al,11who reported that eclampsia

was more frequent in women with the HELLP syndrome

than in those without the HELLP syndrome at 24 to 32

weeks gestation. This may be related to a bias in their re-

cruitment, because 13 (93%) of the 14 women with

eclampsia before 28 weeks had the HELLP syndrome.11

Although the rate of DIC in our study appeared to be

higher in women with the HELLP syndrome (13%) than

in those with severe preeclampsia (0%), this difference

was not statistically significant. We cannot, however, ex-

clude a type II statistical error because the estimated

power analysis is 0.54. Moreover, these findings are in

agreement with those of Martin et al,7who reported DIC

rates of 12% in women with the HELLP syndrome, classes1 and 2 (eg, platelet count


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should, however, caution that women with DIC should

not be managed expectantly.

Magann et al,16 in a randomized study, analyzed the

usefulness of dexamethasone (20 mg/d) administered

until delivery to 25 women with the HELLP syndrome.

They found a significantly increased entry-to-delivery

interval in treated women in comparison with nontreated

women (41 15 vs 15 4.5 hours, P< .01). This, in turn,

should have a beneficial effect on neonatal outcome. Re-cently, Tompkins and Thiagarajah,17 in a retrospective

study, reported a beneficial effect of corticosteroid treat-

ment given to enhance fetal lung maturity on laboratory

parameters of women with the HELLP syndrome.17 The

number of patients admitted before 28 weeks gestation,

their clinical course, and the neonatal outcome, however,

were not provided in either study.16, 17

On the basis of our results and the data reported in the

literature,14-17 expectant management may be beneficial

in some women with the HELLP syndrome at or before

28 weeks gestation, as reported for women with severe

preeclampsia in the second trimester in the absence of

the HELLP syndrome.5 The ideal approach to answer thisimportant clinical question would be a randomized trial

comparing outcomes for women managed expectantly by

means of high-dose corticosteroid therapy with outcomes

for those managed by immediate delivery.

REFERENCES

1. The American College of Obstetricians and Gynecologists. Hy-pertension in pregnancy. Washington: The College; 1996. Tech-nical Bulletin No.: 219.

2. Sibai BM, Taslimi M, Abdella TN, Brooks TF, Spinnato JA, An-derson GD. Maternal and perinatal outcome of conservativemanagement of severe preeclampsia in midtrimester. Am J Ob-stet Gynecol 1985;152:32-7.

3. Pattinson RC, Odendaal HJ, Du Toit R. Conservative manage-

ment of severe proteinuric hypertension before 28 weeks gesta-tion. S Afr Med J 1988;73:516-8.

4. Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versusexpectant management of severe preeclampsia at 28 to 32weeks gestation: a randomized controlled trial. Am J Obstet Gy-necol 1994;171:818-22.

5. Sibai BM, Akl S, Fairlie F, Moretti M. A protocol for managing se-vere preeclampsia in the second trimester. Am J Obstet Gynecol1990;163:733-8.

6. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Fried-man SA. Maternal morbidity and mortality in 442 pregnancieswith hemolysis, elevated liver enzymes, and low platelets(HELLP syndrome). Am J Obstet Gynecol 1993;169:1000-6.

7. Martin JN Jr, Rinehart BK, May WL, Magann EF, Terrone DA,Blake PG. The spectrum of severe preeclampsia: comparativeanalysis by HELLP (hemolysis, elevated liver enzyme levels, andlow platelet count) syndrome classification. Am J Obstet Gy-

necol 1999;180:1373-84.8. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility

of strict diagnostic criteria for the HELLP (hemolysis, elevatedliver enzymes, and low platelets) syndrome. Am J Obstet Gy-necol 1996;175:460-4.

9. Sibai BM. The HELLP syndrome (hemolysis, elevated liver en-zyme levels, and low platelets): much ado about nothing? Am JObstet Gynecol 1990;162:311-6.

10. Friedman SA, Schiff E, Lubarsky SL, Sibai BM. Expectant man-agement of severe preeclampsia remote from term. Clin ObstetGynecol 1999;42:470-8.

11. Martin JN Jr, Perry KG, Miles JF, Blake PG, Magann EF, RobertsWE, Martin RW. The interrelationship of eclampsia, HELLP syn-drome, and prematurity: cofactors for significant maternal andperinatal risk. Br J Obstet Gynaecol 1993;100:1095-100.

12. Magann EF, Perry KG, Chauhan SP, Graves GR, Blake PG, Mar-tin JN Jr. Neonatal salvage by weeks gestation in pregnancies

complicated by HELLP syndrome. J Soc Gynecol Investig 1994;1:206-9.

13. Abramovici D, Friedman SA, Mercer BM, Audibert F, Kao L,Sibai BM. Neonatal outcome in severe preeclampsia at 24 to 36weeks gestation: does the HELLP (hemolysis, elevated liver en-zymes, and low platelet count) syndrome matter? Am J ObstetGynecol 1999;180:221-5.

14. Visser W, Wallenburg HCS. Temporising management of severepre-eclampsia with and without the HELLP syndrome. Br J Ob-stet Gynaecol 1995;102:111-7.

15. van Pampus MG, Wolf H, Westenberg SM, van der Post JAM,Bonsel GJ, Treffers PE. Maternal and perinatal outcome after ex-pectant management of the HELLP syndrome compared withpreeclampsia with HELLP syndrome. Eur J Obstet Gynecol Re-prod Biol 1998;76:31-6.

16. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Mar-tin JN Jr. Antepartum corticosteroids: disease stabilization in pa-

tients with the syndrome of hemolysis, elevated liver enzymes,and low platelets (HELLP). Am J Obstet Gynecol 1994;171:1148-53.

17. Tompkins MJ, Thiagarajah S. HELLP (hemolysis, elevated liverenzymes, and low platelet count) syndrome: the benefit of cor-ticosteroids. Am J Obstet Gynecol 1999;181:304-9.

Volume 183, Number 6 Haddad et al 1479Am J Obstet Gynecol

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