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Research Article | Volume 14 Issue: 4 (Jul-Aug, 2024) | Pages 1134 - 1137
Comparative Study of Serum Homocysteine Levels in Preeclamptic and Normotensive Pregnant Women and Their Association with Maternal and Fetal Outcomes
 ,
 ,
1
Postgraduate, Department of Obstetrics and Gynaecology, Chalmeda Anandrao Institute of Medical Sciences, Karimnagar, Telangana, India
2
Assistant Professor, Department of Obstetrics and Gynaecology, Government Medical College and General Hospital, Kamareddy, Telangana, India
Under a Creative Commons license
Open Access
Received
July 2, 2024
Revised
July 12, 2024
Accepted
July 21, 2024
Published
July 30, 2024
Abstract

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with significant maternal and fetal morbidity. Homocysteine, a sulfur-containing amino acid, has been implicated in endothelial dysfunction and vascular pathology. This study aimed to evaluate and compare serum homocysteine levels in preeclamptic and normotensive pregnant women and correlate these levels with disease severity and outcomes. Methods: This prospective case-control study was conducted at Chalmeda Anand Rao Institute of Medical Sciences, Telangana, from September 2022 to February 2024. A total of 80 pregnant women between 26–40 weeks of gestation were enrolled, including 40 preeclamptic (cases) and 40 normotensives (controls). Detailed clinical evaluation, blood pressure measurement, and biochemical investigations including serum homocysteine estimation were performed. Maternal and fetal outcomes were recorded. Statistical analyses included t-tests, chi-square tests, and Pearson correlation. Results: The mean serum homocysteine level was significantly higher in the preeclamptic group (15.52 ± 4.80 µmol/L) compared to controls (10.42 ± 3.64 µmol/L, p < 0.001). Hyperhomocysteinemia (>15 µmol/L) was observed in 65% of cases and 10% of controls. A strong positive correlation was noted between homocysteine levels and systolic (r = 0.512) and diastolic blood pressure (r = 0.482). Adverse maternal and fetal outcomes, including preterm delivery, low birth weight, increased NICU admissions, and maternal complications, were more prevalent in the preeclamptic group. Conclusion: Elevated serum homocysteine levels are significantly associated with preeclampsia and correlate with disease severity and adverse outcomes. Homocysteine may serve as a potential biochemical marker for early identification and risk stratification of preeclampsia.

Keywords
INTRODUCTION

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. It contributes significantly to maternal and fetal morbidity and mortality, particularly in low- and middle-income countries. Despite extensive research, the exact etiology of preeclampsia remains incompletely understood. However, emerging evidence suggests that endothelial dysfunction and impaired placental perfusion play pivotal roles in its pathogenesis.

 

Homocysteine, a sulfur-containing amino acid generated during methionine metabolism, has been increasingly recognized as a marker of vascular endothelial injury. Elevated serum homocysteine levels, or hyperhomocysteinemia, are known to promote oxidative stress, thrombogenesis, and vasoconstriction—all of which may contribute to the pathophysiological changes observed in preeclampsia. Several studies have demonstrated significantly higher homocysteine concentrations in women with preeclampsia compared to normotensive pregnant women [1–5].

 

Rajkovic et al. first reported elevated homocysteine levels in preeclamptic patients, suggesting a possible link to the disorder’s vascular pathology [1]. Powers et al. further confirmed this association, highlighting endothelial activation as a concurrent finding [2]. Cotter et al. observed that raised homocysteine levels in early pregnancy may be predictive of severe preeclampsia later in gestation [3]. Similarly, Qiu et al. and Gurbuz et al. found a strong correlation between hyperhomocysteinemia and both early-onset preeclampsia and disease severity [4,5].

 

In light of these findings, the present study was undertaken to assess and compare serum homocysteine levels in preeclamptic and normotensive pregnant women, and to examine their association with maternal and fetal outcomes.

METHODOLOGY

Study Design and Setting

This was a prospective case-control study conducted in the Department of Obstetrics and Gynaecology at Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar, Telangana. The study period extended from September 2022 to February 2024.

 

Study Population

A total of 80 pregnant women between 26 and 40 weeks of gestation were enrolled in the study. Participants were divided into two groups:

 

Cases: 40 pregnant women diagnosed with preeclampsia, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on two occasions at least 4 hours apart, along with proteinuria ≥1+ on dipstick or ≥300 mg in a 24-hour urine collection.

 

Controls: 40 normotensive pregnant women without any medical or obstetric complications.

 

Inclusion Criteria

  • Age between 18 and 35 years
  • Singleton pregnancy
  • Gestational age between 26–40 weeks
  • For cases: meeting diagnostic criteria for preeclampsia
  • For controls: normal blood pressure and absence of proteinuria

 

Exclusion Criteria

·        Chronic hypertension

  • Diabetes mellitus
  • Multiple gestation
  • Systemic lupus erythematosus (SLE)
  • Thrombophilia
  • Severe anemia
  • Abruptio placentae or other causes of vaginal bleeding

 

Data Collection

A detailed history, physical examination, and relevant obstetric and laboratory evaluations were conducted. Demographic details, booking status, parity, gestational age, and body mass index (BMI) were recorded. Blood pressure measurements were taken using standard techniques.

 

Laboratory Analysis

Venous blood samples were collected under aseptic precautions. Serum homocysteine levels were estimated using the ADVIA Centaur HCY assay, a direct chemiluminescent technology. Homocysteine levels >15 µmol/L were considered indicative of hyperhomocysteinemia.

 

Maternal and Fetal Outcome Measures

Data on gestational age at delivery, mode of delivery, birth weight, NICU admissions, and maternal complications (e.g., HELLP syndrome, antepartum hemorrhage) were recorded.

 

Statistical Analysis

Data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent samples t-test. Categorical variables were compared using the chi-square test or Fisher’s exact test. Pearson correlation was used to evaluate the association between serum homocysteine and blood pressure parameters. A p-value <0.05 was considered statistically significant.

 

Ethical Considerations

The study was approved by the Institutional Ethics Committee of Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar (Ref No: CAIMS/IEC/PG/093/2022). Informed written consent was obtained from all participants prior to enrollment.

RESULTS

A total of 80 pregnant women were included in this study, comprising 40 women with preeclampsia (cases) and 40 normotensive pregnant women (controls). The groups were comparable in terms of age and gravida distribution.

 

Demographic Characteristics

The mean age of participants in the preeclampsia group was 25.3 ± 4.40 years, while in the control group it was 26.53 ± 3.98 years. A significantly higher proportion of unbooked cases was noted among preeclamptic women (60%) compared to controls (35%). Primigravida status was more common in both groups but slightly higher in cases (70%) than controls (62.5%). A greater proportion of women in the preeclamptic group had a BMI ≥ 25 (55% vs. 40%) (Table 1).

 

Table 1: Demographic Characteristics of Study Participants

Variable

Cases (n = 40)

Controls (n = 40)

Mean Age (years)

25.3 ± 4.40

26.53 ± 3.98

Booked Status

16 (40%) Booked

26 (65%) Booked

Gravida

28 (70%) Primi

25 (62.5%) Primi

BMI ≥ 25

22 (55%)

16 (40%)

 

Blood Pressure and Severity of Preeclampsia

Among the preeclamptic women, 75% had systolic blood pressure (SBP) ≥ 150 mmHg, whereas only 5% of normotensive women had similar readings. The severity classification showed that 40% of preeclamptic patients had severe preeclampsia, while 60% had non-severe forms. Data on diastolic blood pressure (DBP) ≥ 100 mmHg were not explicitly shown in the records (Table 2).

 

Table 2: Blood Pressure and Severity of Preeclampsia

Parameter

Cases (n = 40)

Controls (n = 40)

SBP ≥ 150 mmHg

30 (75%)

2 (5%)

DBP ≥ 100 mmHg

Data not shown explicitly

Data not shown explicitly

Severe Preeclampsia

16 (40%)

Not Applicable

Non-severe Preeclampsia

24 (60%)

Not Applicable

 

Gestational Age at Delivery

A significant difference was observed in the distribution of gestational age. Preterm delivery (<37 weeks) was more common in preeclamptic women, with 22.5% delivering between 28–32 weeks and 37.5% between 33–36 weeks. In contrast, a higher proportion of normotensive women delivered at term (37–40 weeks) (45%) (Table 3).

 

Table 3: Gestational Age Distribution

Gestational Age (weeks)

Cases (n = 40)

Controls (n = 40)

28–32

9 (22.5%)

8 (20%)

33–36

15 (37.5%)

4 (10%)

37–40

16 (40%)

18 (45%)

 

Serum Homocysteine Levels

The mean serum homocysteine level was significantly elevated in the preeclamptic group (15.52 ± 4.80 µmol/L) compared to controls (10.42 ± 3.64 µmol/L). Hyperhomocysteinemia (defined as >15 µmol/L) was observed in 65% of cases and only 10% of controls. A statistically significant positive correlation was found between serum homocysteine levels and both SBP (r = 0.512, p < 0.001) and DBP (r = 0.482, p < 0.001) among the preeclamptic group. No such correlation was noted in controls (Table 4).

 

Table 4: Serum Homocysteine Levels

Parameter

Cases (n = 40)

Controls (n = 40)

Mean Serum Homocysteine (µmol/L)

15.52 ± 4.80

10.42 ± 3.64

Hyperhomocysteinemia (>15 µmol/L)

26 (65%)

4 (10%)

Correlation with SBP (Pearson’s r)

r = 0.512 (p < 0.001)

Not significant

Correlation with DBP (Pearson’s r)

r = 0.482 (p < 0.001)

Not significant

 

Maternal and Fetal Outcomes

Adverse maternal and perinatal outcomes were more prevalent among preeclamptic women. Preterm delivery occurred in 47.5% of cases compared to 20% of controls. The rate of lower segment cesarean section (LSCS) was higher in the preeclampsia group (67.5% vs. 45%). Low birth weight (<2.5 kg) was noted in 52.5% of cases versus 20% of controls. Neonatal intensive care unit (NICU) admissions were also more frequent in the case group (37.5% vs. 15%). Maternal complications, including HELLP syndrome and antepartum hemorrhage, occurred in 30% of preeclamptic women, whereas no such complications were reported in the control group (Table 5).

 

Table 5: Maternal and Fetal Outcomes

Outcome

Cases (n = 40)

Controls (n = 40)

Preterm Delivery

19 (47.5%)

8 (20%)

LSCS Rate

27 (67.5%)

18 (45%)

Birth Weight < 2.5 kg

21 (52.5%)

8 (20%)

NICU Admission

15 (37.5%)

6 (15%)

Maternal Complications

12 (30%) (e.g., HELLP, APH)

None reported

DISCUSSION

This study found a significant elevation in serum homocysteine levels among preeclamptic women compared to normotensive pregnant women. Hyperhomocysteinemia was observed in 65% of the preeclampsia group, and elevated levels correlated positively with both systolic and diastolic blood pressure. These findings reinforce the growing body of evidence that implicates homocysteine as a contributor to the pathophysiology of preeclampsia.

 

Preeclampsia is increasingly recognized as an endothelial cell disorder, with vascular dysfunction playing a central role in its development [8]. The proposed mechanisms include increased oxidative stress, inflammatory responses, and impaired placental perfusion [6,9]. Elevated homocysteine levels may exacerbate endothelial injury, promoting vasoconstriction, platelet aggregation, and thrombogenesis—all of which can contribute to the clinical manifestations of preeclampsia [8,9].

 

Homocysteine metabolism is closely linked with folate and vitamin B12 levels. Deficiencies in these micronutrients can impair remethylation pathways, leading to increased homocysteine concentrations. Yadav et al. recently demonstrated that women with preeclampsia had significantly lower folate and B12 levels and higher homocysteine levels than healthy controls, underscoring the nutritional and metabolic basis of the disorder [7]. Makedos et al. also observed similar associations, suggesting that supplementation may play a preventive role [10].

 

Vollset et al., in a large population-based study, confirmed that hyperhomocysteinemia during pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, placental abruption, and fetal growth restriction [11]. Additionally, Walker emphasized the multifactorial nature of preeclampsia, involving genetic, immunological, and environmental factors [12].

CONCLUSION

This study establishes a significant association between elevated serum homocysteine levels and preeclampsia in pregnant women. The prevalence of hyperhomocysteinemia was markedly higher among preeclamptic women and correlated positively with both systolic and diastolic blood pressure, as well as the severity of the condition. Additionally, elevated homocysteine levels were linked to adverse maternal and fetal outcomes, including increased rates of preterm delivery, low birth weight, and NICU admissions. These findings suggest that serum homocysteine could serve as a useful biochemical marker for identifying women at risk of preeclampsia and predicting its severity. Early detection and targeted intervention may improve maternal and perinatal outcomes.

REFERENCES
  1. Rajkovic A, Catalano PM, Malinow MR. Elevated homocysteine levels with preeclampsia. Obstet Gynecol. 1997;90(2):168–71.
  2. Powers RW, Evans RW, Majors AK, Ojimba JI, Ness RB, Crombleholme WR, et al. Plasma homocysteine concentration is increased in preeclampsia and associated with evidence of endothelial activation. Am J Obstet Gynecol. 1998;179(6 Pt 1):1605–11.
  3. Cotter AM, Molloy AM, Scott JM, Daly SF. Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia. Am J Obstet Gynecol. 2001;185(4):781–5.
  4. Qiu C, Hevner K, Enquobahrie DA, Williams MA. A case-control study of maternal blood concentrations of homocysteine and early-onset preeclampsia. Clin Biochem. 2004;37(4):313–8.
  5. Gurbuz A, Karateke A, Mengulluoglu M. Elevated plasma homocysteine levels in preeclampsia and eclampsia. Int J Gynaecol Obstet. 2004 Nov;87(2):165-6. doi: 10.1016/j.ijgo.2004.06.024. PMID: 15491570..
  6. Ramma W, Ahmed A. Is inflammation the cause of pre-eclampsia? Biochem Soc Trans. 2011;39(6):1619–27.
  7. Yadav BK, Maskey S, Bhattarai A, Pradhananga S, Shakya S, Regmi A. Association of serum homocysteine with vitamin B12 and folate levels in women with pre-eclampsia in a tertiary health care center in Nepal. BMC Womens Health. 2024 Aug 9;24(1):451. doi: 10.1186/s12905-024-03284-9. PMID: 39123143; PMCID: PMC11311945.
  8. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989 Nov;161(5):1200-4. doi: 10.1016/0002-9378(89)90665-0. PMID: 2589440.
  9. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol. 1998;179(5):1359–75.
  10. Makedos G, Papanicolaou A, Hitoglou A, Kalogiannidis I, Makedos A, Vrazioti V, Goutzioulis M. Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia. Arch Gynecol Obstet. 2007 Feb;275(2):121-4. doi: 10.1007/s00404-006-0223-2. Epub 2006 Aug 29. PMID: 16941105.
  11. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, Monsen AL, Ueland PM. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr. 2000 Apr;71(4):962-8. doi: 10.1093/ajcn/71.4.962. PMID: 10731504.
  12. Walker JJ. Pre-eclampsia. Lancet. 2000 Oct 7;356(9237):1260-5. doi: 10.1016/S0140-6736(00)02800-2. PMID: 11072961.
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