In this study, the women with AFLP were associated with hypoglycemia, hyperbilirubinemia, AKI, DIC and sepsis, whereas those with HELLP syndrome were associated with hypertension on admission, preeclampsia and low platelet counts. We also demonstrated a signiﬁcantly higher rate of twin pregnancy in the AFLP group. However, more neonatal complications were noted in the HELLP syndrome group, such as SGA, RDS, and neonatal sepsis. Accordingly, clinical and laboratory evidence of hypoglycemia, hyperbilirubinemia, hypofibrinogenemia, AKI, DIC and sepsis may help to differentiate AFLP from HELLP syndrome.
AFLP and HELLP syndrome differed in the magnitude of systemic involvement. Multiple organ dysfunction was more likely to occur in the patients with AFLP. Hypoglycemia results from impaired hepatic glycogenolysis, and AFLP with hepatic steatosis can inhibit bilirubin clearance resulting in hyperbilirubinemia and jaundice19. AKI can be caused by defective renal fatty acid oxidation, and fatty degeneration in renal tubules20 while severe hepatic impairment can also lead to hepatorenal syndrome. The major cause of coagulopathy resulting in DIC is the reduction in hepatic production of fibrinogen and other procoagulant proteins19. Compared to the women with AFLP, those with HELLP syndrome had a higher BMI at delivery, which is consistent with previous studies that obesity is one of the risk factors of HELLP syndrome21.
Even with the various maternal complications associated with AFLP, neonatal morbidities in the AFLP group were not as high as those in the HELLP syndrome group. This may be because the toxic unoxidized fatty acids due to LCHAD deficiency in the AFLP group were transferred to the mother through the placenta instead of accumulating in the fetus, thereby not increasing neonatal morbidities compared to the HELLP syndrome group.
As would be anticipated, HELLP syndrome was more likely to occur in the patients with preeclampsia and a low platelet count. Although the relationship between HELLP syndrome and preeclampsia is still controversial, HELLP syndrome is usually considered to be a severe form or a variant of preeclampsia11. In addition, HELLP is related to endothelial injury and microangiopathic platelet consumption, which results in thrombocytopenia7.
Twin pregnancy has been reported to be a risk factor for both AFLP and HELLP syndrome9. However, in this head-to-head comparison study, the rate of twin pregnancy in the AFLP group was significantly higher than that in the HELLP syndrome group. Most previous studies have indicated that fetal LCHAD deficiency4 and other types of deficiencies in fetoplacental mitochondrial oxidation, such as short-chain acyl-coenzyme dehydrogenase deficiency and carnitine palmitoyltransferase deficiency are related to the development of AFLP22,23. Accordingly, it has been hypothesized that twice the amount of upstream metabolites accumulate in the circulation of mothers with twins due to these enzyme deficiencies, resulting in a lower threshold to express clinical symptoms and signs in patients with AFLP.
Another important finding of this study is the significantly higher rate of SGA neonates born to the mothers with HELLP syndrome. Although twin pregnancy is known to be a key factor leading to SGA, we found a higher rate of twin pregnancy in the AFLP group rather than the HELLP syndrome group. This could be explained by the abnormal placentation in patients with HELLP syndrome. Alterations in platelet activation, increases in pro-inflammatory cytokines, and segmental vasospasm with vascular endothelial damage could impair nutritional exchange through the feto-placental unit and subsequently result in SGA3,5. In addition, higher rates of neonatal RDS and sepsis were also noted in the HELLP syndrome group. A correlation between SGA and RDS has been reported, possibly because intrauterine lung development can be adversely affected by SGA due to reduced substrate supply, fetal hypoxemia and hypercortisolemia24. The possible mechanism of increased sepsis in SGA neonates is the delayed immune system development, which results in a higher rate of neonatal infection25.
The strengths of this study include that this was a head-to-head comparison study of both maternal and neonatal outcomes. Moreover, the data were collected from one medical center, which could minimize management bias in different institutions. Nevertheless, there are several limitations to this study. First, the data were collected from one medical center, and thus the case numbers were limited even a near 17-year span. Second, advances in maternal and neonatal care in the recent two decades may have resulted in different maternal and neonatal outcomes.