Women with HELLP syndrome were significantly more likely than those with ELLP syndrome to have received magnesium sulfate (76% [98/129] compared with 62% [50/81], P=.028). No other significant differences in management were seen between the women with either HELLP or ELLP syndrome (data not shown) and therefore the management of these women has been presented together. Of the women diagnosed antenatally with HELLP or ELLP syndrome: 51% (71/138) had a planned management of immediate delivery and delivered a median of 3 hours 41 minutes after diagnosis (range 38 minutes to 32 hours 22 minutes) at a median gestation of 35 weeks (range 22–41 weeks), 91% (63/69) by cesarean delivery; 43% (60/138) had a planned management of delivery within 48 hours and delivered a median of 11 hours 40 minutes after diagnosis (range 1 hour 28 minutes to 95 hours 56 minutes) at a median gestation of 35 weeks (range 22–40 weeks), 68% (40/59) by cesarean delivery; only seven of 138 (three had HELLP and four had ELLP syndrome) had a planned attempt at expectant (conservative) management; these women were diagnosed at a median of 29 weeks of gestation (range 24–39 weeks) and delivered a median of 3 days after diagnosis (range 1–12 days), all by cesarean delivery (indication maternal compromise). Women who had a planned management of delivery within 48 hours were more likely than those who had planned immediate delivery to be nulliparous (83% [50/60] compared with 68% [48/71], P=.039), but no other differences in characteristics were found between these women. Overall, 47% (99/209) of the women with HELLP or ELLP syndrome received corticosteroids (only three for maternal indications, two of whom were diagnosed postpartum) and 80% (166/208) were given antihypertensive medication.
Table 4 summarizes the main maternal outcomes of women with both HELLP and ELLP syndrome. Compared with the women with ELLP syndrome, those with HELLP syndrome were more likely to have a blood transfusion and were more likely to have severe morbidity, although the proportion admitted to level 2 or level 3 critical care14 (which we will refer to as intensive care unit [ICU]), the duration of stay in ICU and proportion with eclampsia did not significantly differ. Although there were no maternal deaths among the women diagnosed with ELLP syndrome, one woman with HELLP syndrome died (case fatality 0.8%, 95% CI 0.02–4.2%).
No significant differences were found between the women who had a planned management of delivery within 48 hours of diagnosis and those who had a planned management of immediate delivery in terms of the proportion who received blood products (37% [21/57] compared with 33% [23/69], P=.681); were admitted to the ICU (57% [34/60] compared with 61% [43/71], P=.652); or experienced severe morbidity (10% [6/60] compared with 4% [3/71], P=.300). Of the seven women who had a planned attempt at expectant management, two received blood products, five were admitted to the ICU, but none experienced severe morbidity or died.
No significant differences were found between the women with HELLP syndrome who were given blood products and those who were not in terms of their median lowest platelet count recorded (46×109/L, range 12–96 compared with 55×109/L, range 20–99, P=.0.62) or the proportion with a lowest recorded platelet count of less than 50×109/L (56% [32/57] compared with 44% [30/68], P=.181). There were also no significant differences apparent between the women with HELLP syndrome who were admitted to the ICU and those who were not in terms of their median lowest platelet count recorded (49×109/L, range 20–99 compared with 50×109/L, range 12–96, P=.912) or the proportion with a lowest recorded platelet count of less than 50×109/L (51% [42/82] compared with 49% [23/47], P=.803). Similarly, no significant differences were seen between the women with HELLP syndrome who experienced severe morbidity and those who did not in terms of their median lowest platelet count recorded (46×109/L, range 22–80 compared with 51×109/L, range 12–99, P=.48) or the proportion with a lowest recorded platelet count of less than 50×109/L (59% [10/17] compared with 49% [55/112], P=.455).
Of the women with HELLP syndrome, two had late fetal demises and two had their pregnancy terminated because of HELLP syndrome before 24 weeks of gestation. The remaining 125 women with HELLP syndrome gave birth to a total of 135 neonates (116 singleton, eight twin, and one triplet pregnancy), whereas the 81 women with ELLP syndrome gave birth to a total of 87 neonates (75 singleton, six twin pregnancies). There were two stillbirths, no early neonatal deaths, two late neonatal deaths, and one post neonatal death among the 135 neonates born to women with HELLP syndrome, equating to a perinatal morality rate of 15 per 1,000 total births (95% CI 2–53); a late neonatal mortality rate of 15 per 1,000 live births (95% CI 2–53); and a postneonatal mortality rate of eight per 1,000 live births (95% CI 0.2–41). Of the 87 neonates born to women with ELLP syndrome, there were no stillbirths, one early neonatal death, and one postneonatal death, equating to a perinatal mortality rate of 12 per 1,000 total births (95% CI 0.3–62) and a postneonatal mortality rate of 12 per 1,000 live births (95% CI 0.3–62). There were no statistically significant differences in these rates between HELLP syndrome and ELLP syndrome but note the low statistical power of this comparison. All of the neonates who died apart from one were born very preterm (less than 28 weeks of gestation).
Women with HELLP syndrome and those with ELLP syndrome both had a similarly high preterm (less than 37 weeks of gestation) birth rate (59% [74/125] compared with 72% [58/81], respectively, P=.070), mainly iatrogenic (95% [126/132]). The proportion of neonates with major complications such as respiratory distress syndrome, chronic lung disease, severe infection, and necrotizing enterocolitis was also similar between the neonates born to women with both HELLP and ELLP syndrome (10% [13/131] compared with 7% [6/86], P=.453) and higher than the rate reported in the control neonates (1% [6/480], P<.001), although this difference disappeared after controlling for gestational age at delivery. Having controlled for maternal age, ethnicity, socioeconomic status, body mass index, smoking status, and parity, the proportion of neonates who were small for gestational age was similar between the neonates born to women with both HELLP and ELLP syndrome (26% [35/135] compared with 30% [26/86], P=.701) and significantly higher than the proportion seen in the control infants (8% [41/483], P<.001).
There were no significant differences between the neonates born to women who had a planned management of delivery within 48 hours of diagnosis and those born to women who had a planned management of immediate delivery in terms of the proportion that were born preterm (67% [43/64] compared with 71% [52/73], P=.626); were small for gestational age (20% [13/64] compared with 26% [19/73], P=.431), had major complications (6% [4/64] compared with 11% [8/73], P=.342), or who died perinatally (zero of 64 compared with one of 72, P=1.000). Of the seven neonates born to the women who had a planned attempt at expectant management, none died, but two had major complications relating to preterm birth and three were small for gestational age.
Our incidence estimates indicate the rarity of HELLP syndrome and ELLP syndrome and are lower than frequently quoted rates.7,15 There may be a number of reasons for this difference, including variable and inconsistent diagnostic criteria3; we used a case definition comparable to the strict criteria proposed by Sibai et al.3,16 Other methodologic differences may also explain our lower incidence estimates. The existing literature is dominated by retrospective studies undertaken in single tertiary referral centers. Such studies tend to underestimate the denominator population, leading to an overestimate of incidence. They also tend to rely on coded data from routine hospital administrative systems, which may lead to inaccurate case ascertainment.17
As a result of the rarity of HELLP and ELLP syndrome, we had limited power to analyze risk factors. Nevertheless, consistent with the hypothesis that the syndrome is part of the spectrum of hypertensive disorders of pregnancy, the factors our study found to be associated with HELLP or ELLP syndrome are the same as many of the reported risk factors for preeclampsia.18–20 It is possible that there has been a decrease in the incidence of the syndrome in the United Kingdom, perhaps because progression from preeclampsia to HELLP syndrome is being more effectively prevented by improved management practices, similar to the decrease in incidence that has been reported for eclampsia.17 We also cannot rule out the possibility that our lower incidence estimates are the result of underreporting of cases, although we have taken steps to minimize this.
There are three main options for the management of women who develop the syndrome antenatally: immediate delivery, delivery within 48 hours, and prolonging pregnancy (expectant management). We found that expectant management is rarely used in the United Kingdom and therefore cannot provide clear evidence of the risks or benefits of this approach. However, we were able to compare the maternal and neonatal outcomes of planned delivery within 48 hours compared with planned immediate delivery, finding no significant differences. This suggests that a short delay in delivery may be considered if the maternal and fetal status is reassuring, although we acknowledge that even in this national study, the analysis may not have sufficient power to detect real differences as statistically significant. A short delay is important to consider in situations where fetal lung maturation can be enhanced by the administration of corticosteroids.21 Current U.K. guidelines recommend two main situations where this is the case: when a woman is at risk of preterm birth up to 34+6 weeks of gestation and when a cesarean delivery is planned before 38+6 weeks of gestation.22 Our study suggests that currently corticosteroids are rarely used in the United Kingdom to improve maternal outcome in HELLP syndrome.
In keeping with other studies,23–26 we found that women with HELLP syndrome were more likely than those with ELLP syndrome to experience severe morbidity and require blood transfusion. This finding supports Sibai et al’s26 assertion of the importance of using strict diagnostic criteria for reporting and managing women with HELLP syndrome. Nevertheless, it is important to note that both groups experienced severe complications including admission to the ICU, emphasizing that both should be considered as serious pregnancy complications. The occurrence of eclampsia in both groups also highlights the importance of considering seizure prophylaxis in these women.
Consistent with other studies,27,28 we found that women with both HELLP and ELLP syndrome have a similarly increased risk of adverse infant outcomes. Although this appears primarily to be associated with iatrogenic preterm birth, our study suggests that women with both HELLP and ELLP syndrome also have an increased risk of having a small-for-gestational-age neonate; this should be taken into account when considering further research on expectant management.
In summary, where there are sound reasons that a delay in delivery of women with HELLP or ELLP syndrome may be beneficial, eg, to allow administration of corticosteroids for fetal lung maturation, this study suggests that a short delay, of up to 48 hours, may be considered. Current U.K. guidelines recommend corticosteroids when there is a risk of delivery before 35 completed weeks of gestation or planned cesarean delivery at less than 39 completed weeks of gestation. Although we cannot comment on whether ELLP cases proceed to HELLP or whether they are different entities, it is clear that women with ELLP as well as HELLP have severe additional complications, and thus ELLP should not be managed as a less severe form of HELLP. In particular, there is a high rate of eclampsia among both women with ELLP and HELLP; thus, obstetricians should consider magnesium sulfate prophylaxis alongside delivery planning.
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© 2014 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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