Relationship of Severe Maternal Morbidity and Maternal Mortality to Serum Lipids in Hypertensive Disorders of Pregnancy

Background: Hypertensive disorders of pregnancy (HDP) are associated with a large burden of maternal morbidity and mortality. Whether lipids affect the maternal outcome in these cases is not well known. Research goes on. Objective: Study was conducted to know relationship between lipid abnormalities and severe morbidity, mortality in women with hypertensive disorders of pregnancy. Methodology: In the present prospective study of women with singleton pregnancy of gestational 28 weeks and beyond with hypertensive disorders ,fasting serum lipids, cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were estimated at entry and repeated every 7 days. Cases were observed for placental abruption, renal failure, pulmonary edema, HELLP (Hemolysis, Elevated liver enzymes, and low platelets), partial HELLP or post partum haemorrhage (PPH) and followed up till 7 days postpartum. Results: Occurrence of maternal complications was significantly less (p<0.001) in women who had mild or severe PIH with normal serum lipid levels (p<0.001). In women with mild and , severe preeclampsia with normal lipid levels the occurrence of the complications was significantly less (p<0.001). Only 2 women with eclampsia had normal lipid levels, hence comparison was not possible. Also there was linear relationship between period of gestation, serum lipid abnormalities and severity of maternal morbidities. Between the gestation period from 28-34 weeks, out of 292 women, 167(57.19%) women had lipid abnormalities compared to 222(99.10%) of 224 women between gestational age 34-37 weeks. Of the 964 women with hypertensive disease, four (0.41%) women died. Maternal Mortality Ratio (MMR) was 465.65 amongst HDP, 28.6% of the overall maternal mortality during the study period. Overall MMR during the study period was 200.54. MMR without hypertensive disorders was 163.34. Four women who died had deranged lipids Conclusion: As observed dyslipidemia and severity of hypertensive disorders of pregnancy and complications are closely associated. Further research is needed to uncover these associations.


Introduction
Hypertensive disorders of pregnancy (HDP) are associated with a large burden of maternal morbidity and mortality Roberts [1], Dekkar [2], Farrokh-Eslamlou et al. [3], Bauserman et al. [4], Soni-Trinidad et al. [5] due to the disease itself or the consequences and interventions. In spite of being common disorders, HDP are not very well understood as to why some mothers do well and others do not. Among many causative factors, serum lipids are believed to play an active role in the etiopathogenesis of hypertensive disorders of pregnancy Boden [6], Wakatsuki et al. [7], Herrera [8], Lain et al. [9], Herrera et al. [10], Nickens et al. [11] and may be affect the outcome too. HDP are known to be associated with dyslipidemia, placental dysfunction and endothelial cell activation. Dukić et al. [12], Stocks [13], Szpera-Gozdziewicz et al. [14] whether lipids affect

Material and Methods
The present prospective study of women with singleton pregnancy of gestational age 28 weeks and beyond with pregnancy induced hypertension (PIH-hypertension systolic blood pressure 140 , diastolic 90 or more) or preeclampsia [with proteinuria of more than 300mg/l in 24 hrs or 30 mg/dl (1+ dipstick) detected in random urine] or eclampsia (hypertension associated with seizures non-attributable to any other cause) was carried out over a period of two years at a rural institute after taking informed consent.
PIH and preeclampsia were further subdivided into mild (diastolic Blood Pressure 90-110 mm Hg or less), and severe (diastolic BP >110 mm Hg). Fasting serum lipids, cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were estimated at entry and repeated every 7 days.
Cases were observed for placental abruption, renal failure, pulmonary edema, HELLP (Hemolysis, Elevated liver enzymes, and low platelets), partial HELLP or post partum haemorrhage (PPH) and followed up till 7 days postpartum.

Journal of Gynecology and Women's Health
There was linear relationship between period of gestation, serum lipid abnormalities and severity of maternal morbidities. Between the gestation period from 28-34 weeks, out of 292 women, 167(57.19%) women had lipid abnormalities, compared to 222(99.10%) of 224 women between gestational age 34-37 and 432(68.03%) of 635women of gestation >37 weeks. Of the 964 women with hypertensive disease four (0.41%) women died. Amongst HDP cases. Maternal Mortality Ratio (MMR) was 465.65, 28.6% of the overall maternal mortality during the study period. Overall MMR during the study period was 200.54. MMR without these disorders was 163.34. All of the 4 women who died had deranged lipids; one was a 27 year old second para with severe preeclampsia at 28 weeks. She presented in coma and was diagnosed to have cerebral hemorrhage. She had elevated cholesterol, triglycerides. LDL, VLDL below normal HDL levels. The second woman was a 22 years primipara who had post partum eclampsia with HELLP, DIC and atonic PPH. She had elevated cholesterol, triglycerides, and LDL, VLDL and below normal HDL. The third case, a 20 years primipara with eclampsia, died due to intracranial hemorrhage and had elevated cholesterol, triglycerides, LDL, VLDL and normal HDL levels. Fourth woman was 24 years primipara with severe PIH with HELLP with DIC. She had elevated cholesterol, triglycerides, and LDL, VLDL below normal HDL levels. All the eclamptic women (2 of 4 who died) had severely deranged serum lipid levels. (Table  3)

Discussion
In spite of being a common entity, known since ages, with dangerous implications for the mother and the baby, hypertensive disorders of pregnancy still remain an unsolved problem. They affect pregnancy in many ways, but not all pregnancies are affected in the same way or to similar extent and research continues.
In the present study it was found that there was significant relationship between lipid derangements and severity of hypertensive disorders and its impact on severity of morbidity it causes. Among 964 hypertensive women, the most pathological, serum triglycerides were elevated in 890 (92.32%) women. Other lipids deranged were elevated cholesterol in 637 (66.07%) % women, 453 (46.99%) women had elevated VLDL, 181 (18.77%) women had elevated LDL and 99 (10.26%) women had low serum HDL levels. Among all the lipids, LDL correlated best with the risk of complications, placental abruption, PPH, HELLP, partial HELLP, renal failure and pulmonary edema and more research needs to be done.
In one of our earlier studies Chhabra et al. [15], presence of HELLP/partial HELLP was found to be associated with the adverse pregnancy even in cases of mild hypertensive disorders also as reported by some other researchers Ray et al. [16], Ekhator and Ebomoyi [17], Vigil-De Gracia P [18] This suggests that something else is also responsible in the pathogenesis of complications in hypertensive disoeders during pregnancy. It has been reported that the lipids are deranged in all these subjects Ray et al. [16], Ekhator and Ebomoyi [19]. All women who died had severe hypertensive disorders and elevated cholesterol, triglycerides, LDL, VLDL levels while, and 3 had below normal HDL levels.
Mudd et al. [19] have reported that high TG, LDL and Cholesterol are modestly associated with the risk of hypertensive disorders of pregnancy and maternal and fetal/neonatal complications. Scifres et al. [20] found that maternal serum fatty acid binding protein 4 (FABP4) levels are elevated before the clinical onset of preeclampsia which was indirect indication of dyslipidemia having a causative relationship with hypertensive disorders of pregnancy and its complications. Ghio et al. [21] have suggested that increased TG during pregnancy appear to increase risk of preeclampsia and preterm birth. Authors suggested that maternal hypertriglyceridemia had a role in increasing cardiovascular risk later in life and increasing future morbidity. So may be women who have lipid derangements and hypertensive disorders have more chances of cardiovascular disease [22][23][24][25][26][27][28].

Conclusion
As observed dyslipidemia and severity of hypertensive disorders of pregnancy and complications are closely associated. Further research is needed to uncover these associations.