Preeclampsia,periodontitis and their interactions on cardiometabolic risk markers in pregnancy: A case-control study

Abstract

Objective

Preeclampsia and periodontitis are characterised by altered lipid metabolism. Meta-analyses indicate a higher risk of preeclampsia among women with periodontitis, suggesting a plausible biological connection. Understanding their interaction on fasting lipid levels may reveal targets for integrated strategies to reduce maternal and cardiometabolic risks.

Methods

This case-control study was conducted at the Tamale Teaching Hospital from January to September 2025. The study involved 155 pregnant women, ≥ 20 weeks of gestation, including 52 (33.5%) diagnosed with preeclampsia. The women were aged between 19 and 45 years. All the women underwent periodontal examination before a fasting venous blood sample was collected, and then analysed for fasting lipids.

Results

Results showed that preeclampsia was associated [adjusted odds ratio (95%CI)] with periodontal diseases [3.079 (1.414-6.704)] and, particularly, periodontitis [8.905 (3.574-22.188)]. Sub-group analysis showed that the comorbidity of preeclampsia and periodontitis was characterised by higher levels (mmol/L) of total cholesterol (6.4±1.4 vs 4.9±0.7, P<0.010), low-density lipoprotein cholesterol (4.4±1.2 vs 3.0±0.7, P<0.001), and non-high-density lipoprotein cholesterol (5.1±1.3 vs 3.6±0.8, P<0.010) than preeclampsia alone. However, no significant differences in fasting lipids were observed between normotensive pregnant women with and without periodontitis. Moreover, there were significant interactions between preeclampsia and periodontitis on fasting lipid levels.

Conclusion

The study demonstrates a distinct dysregulated lipid profile among preeclamptic women, which appears to be significantly exacerbated by the presence of periodontitis. These results highlight the need for an integrated antenatal care that includes periodontal screening and management, particularly in women at high risk for preeclampsia.

Keywords

preeclampsia periodontitis periodontal diseases cardiometabolic risk factors interactions Ghana

Introduction

Preeclampsia (PE) remains a major contributor to maternal and perinatal morbidity and mortality globally, where sub-Saharan Africa, including Ghana, is disproportionately affected.¹ PE is characterised by new-onset hypertension and proteinuria or end-organ dysfunction after 20 weeks of pregnancy. PE is increasingly recognised not only as an acute obstetric complication but also as a marker of future cardiometabolic risk for the mother and the child.² Altered or dysregulated lipid metabolism is a well-documented feature of PE, with numerous studies, including meta-analyses, reporting elevated maternal triglycerides, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and altered lipoprotein indices compared with normotensive pregnancies. Studies show that these lipid abnormalities are implicated in oxidative stress and endothelial dysfunction, which are central mechanisms in the pathogenesis of preeclampsia and in long-term cardiovascular disease risk.³ PE pregnancies are also characterised by placental hypoxia and inflammation.^4,5

Periodontitis is a chronic, microbially driven inflammatory disease of the supporting tissues of the teeth or periodontium. It is highly prevalent in many low- and middle-income populations (LMICs) and has been documented in Ghanaian communities and antenatal populations.^6,7 Aside from local oral effects, periodontitis induces transient bacteremia, systemic inflammation, and exposure to bacterial products, such as lipopolysaccharides (LPS) from bacterial cell walls, which can disturb maternal immune and metabolic homeostasis.⁸ Previous experimental and clinical studies have associated periodontal inflammation with dyslipidemia, endothelial activation and insulin resistance in pregnant and nonpregnant cohorts, supporting plausible mechanistic pathways by which oral infection could affect pregnancy outcomes.⁹

A growing body of literature has explored the association between maternal periodontitis and adverse pregnancy outcomes, including preeclampsia. Previous meta-analyses and systematic reviews generally report an elevated risk of preeclampsia among women with periodontitis, albeit variations in effect sizes and certainty due to heterogeneity in study designs, periodontal case definitions and confounding control.^10,11 Previous randomised trials of periodontal therapy initiated during pregnancy have shown that non-surgical periodontal treatment is safe and improves oral health; however, evidence that treatment reduces obstetric complications such as preeclampsia remains inconclusive. The possible explanation could be that interventions are often given too late to influence placentation, or that trials were underpowered for hypertensive outcomes.¹² These inconsistencies underscore the need for context-specific, prospective research that integrates standardised oral health assessment with biochemical and obstetric measures.^12,13

In Ghana, routine antenatal care programs rarely integrate lipid profiling or periodontal screening despite compelling evidence of overlapping burdens of infectious and noncommunicable disease risk factors.¹⁴ Local Ghanaian data on the co-occurrence of periodontitis and preeclampsia and on how this interaction may influence maternal lipid profiles are sparse or non-existent.^15,16 Understanding whether periodontitis modifies the relationship between fasting plasma lipid levels and preeclampsia has both mechanistic and public health relevance. If periodontal inflammation amplifies dysregulation of lipid metabolism in preeclampsia, this could identify an actionable target for integrated preventive strategies that reduce immediate obstetric risk and long-term cardiometabolic sequelae among Ghanaian women.¹⁷ Therefore, this study aims to determine the associations between periodontitis, preeclampsia and their interaction on fasting plasma lipid levels among pregnant women.

Materials and methods

Study design and setting

An unmatched case-control study was conducted among pregnant women attending the antenatal clinic at the Tamale Teaching Hospital in the Northern Region of Ghana, between January and September 2025. Tamale is a metropolis and the capital city of the Northern Region of Ghana. Tamale Teaching Hospital serves a mixed urban and peri-urban population and provides tertiary-level care. The hospital has several specialised departments, including functional antenatal and dental clinics that provide obstetric and periodontal examination services to the population of the Northern Region and surrounding regions such as Upper West, Upper East, North-East, and the Savanna regions.

Study population and sample size

The study involved 155 pregnant women, including 52 (33.5%) diagnosed with preeclampsia, while the rest were pregnant women with normotensive pregnancies who served as controls. The women were aged 19 to 45 years in their second or third trimester (≥20 weeks of gestation). The cases and controls (Participants) were recruited consecutively and concurrently from the same clinic to reduce selection bias and bias due to seasonal and environmental factors. Women with systemic diseases unrelated to pregnancy, such as chronic kidney disease, diabetes mellitus, liver disease, tuberculosis or chronic kidney disease and those on lipid-lowering medications, or with recent periodontal therapy or antibiotic use within the past three months, were excluded. The minimum required sample size for this investigation was calculated using the Fleiss formula with Continuity Correction in Epi Info v7 (https://www.cdc.gov/epiinfo/pc.html). Periodontitis was designated the main exposure variable. Reports from previous studies showed that the pooled prevalence of periodontitis among pregnant women in Africa is 58%.^18,19 In addition, a meta-analysis reported that women with periodontitis were over three times more likely to develop preeclampsia (OR 3.18, 95% CI 2.26–4.48).²⁰ Assuming a 95% confidence level, 80% power, and a 1:2 ratio of cases to controls, the sample size required for the study came to 155 participants in total (52 cases and 103 controls).

Diagnosis of preeclampsia

The diagnosis of preeclampsia was based on the definition according to the American College of Obstetricians and Gynaecologists criteria as new-onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on two occasions at least 4 hours apart after 20 weeks of gestation). The hypertension is accompanied by proteinuria (≥300 mg per 24-hour urine collection or ≥1+ on dipstick) or evidence of systemic involvement, such as elevated liver enzymes, thrombocytopenia, renal insufficiency, or pulmonary oedema.²¹ The controls were pregnant women of similar gestational age as the cases who were free of chronic hypertension and did not meet the clinical definition of preeclampsia.

Periodontal examination

A board-certified periodontist diagnosed periodontitis following the standardised procedure and classification by Armitage, Wu.²² Recruited participants underwent a comprehensive periodontal examination (CPE). Periodontal parameters (PP) for selected teeth in each of the four quadrants were recorded using individual periodontal charts. Three previously trained examiners conducted inter-examiner calibration and pretesting. All periodontal parameters were recorded twice independently for each quadrant of the mouth, and the results were compared using periodontal charts until at least 90% of duplicate measurements were within 1 mm. Individual periodontal charts captured parameters for specific teeth in all four quadrants, including bleeding on probing (BOP), clinical attachment loss (CAL), probing pocket depth (PPD), missing teeth, and plaque index (PI). All teeth were examined for each participant. Manual instruments, rather than electronic devices, were used throughout the examination. The instruments, including dental mirrors, periodontal probes, and Naber’s probes, are manufactured by Janbro International, United Kingdom. Bleeding on probing (BOP) was recorded as present or absent. Clinical attachment loss (CAL) was measured from the cementoenamel junction (CEJ) to the base of the periodontal pocket, calculated as probing pocket depth (PPD) minus the CEJ–gingival margin distance in cases without recession, or as the sum of recession and PPD when recession was present. Measurements were taken using a UNC-15 periodontal probe with 1 mm graduations at six sites per tooth (distobuccal, midbuccal, mesiobuccal, distolingual, midlingual, and mesiolingual). A probing force of 0.25 N and a 5° angulation were maintained. X-ray images were not taken to reduce the risk of exposure of the developing foetus to radiation. Periodontitis was defined based on the 2017 World Workshop criteria as the presence of interdental clinical attachment loss (CAL) at two or more non-adjacent teeth or buccal/oral CAL ≥3 mm with a pocket depth (PD) of more than 3 mm.

Blood sample collection and biochemical analysis

The women were prepared a day before with fasting requirements and duration. A 5 mL venous blood sample was collected following an overnight fast of 8–12 hours. The blood samples were dispensed into gel separator tubes and allowed to clot at room temperature. The blood samples were then centrifuged at 3000 rpm for 5 minutes to obtain serum. Serum was separated and aliquoted into Eppendorf tubes and then stored at -20 °C for later analysis. Total cholesterol (TCHOL), high-density lipoprotein (HDL) cholesterol, and triglycerides (TRIG) were determined enzymatically using standard and an automated biochemistry analyser using the manufacturer’s recommended reagents, calibrators, and quality control materials. The LDL cholesterol, non-HDL cholesterol, the atherogenic index (TCHOL/HDL), and the cardiovascular risk (LDL/HDL) were then calculated. All assays were performed under strict quality control with internal and external proficiency checks.

Data collection and variables

Socio-demographic, clinical, and obstetric data were obtained through interviewer-administered questionnaires and reviewing medical records. The dependent variable was preeclampsia (yes/no). The independent variables were periodontitis (yes/no) and their interaction term (preeclampsia × periodontitis), fasting plasma lipid levels, including total cholesterol, LDL, HDL, and triglycerides, as well as their derivatives such as non-HDL cholesterol, total cholesterol/HDL, and LDL/HDL cholesterol ratios. Covariates with confounding potential included maternal age, gestational age, parity, body mass index (BMI), and oral hygiene practices. Potential confounding was addressed using statistical approaches since there was no matching of cases and controls.

Statistical analysis

Data were collected into an MS Excel Spreadsheet and then analysed using IBM SPSS Statistics version 27. The normality of the continuous variables was checked using the Shapiro-Wilk test before being summarised as means ± standard deviations (SD). The categorical variables were summarised as frequencies and percentages. Independent t-tests and one-way ANOVA, with post hoc test for multiple comparisons, were used for group comparisons of continuous variables. Tests of associations were achieved using the Chi-square test or univariable and multivariable binary logistic regression analysis. Multiple linear regression models were fitted with 2-way interaction terms between preeclampsia and periodontitis to evaluate the main and interaction effects of preeclampsia and periodontitis on cardiometabolic factors, adjusting for potential confounders. The interaction term (preeclampsia × periodontitis) was included in the regression model to assess whether the combined presence of both conditions had a multiplicative effect on lipid levels. The assumptions of multivariable linear regression were tested for significant PE*Periodontitis models using the variance inflation factor for multicollinearity diagnosis, the P-P plot for multivariable normality, and the scatter plot (predicted vs residual values) for homoscedasticity. All statistical tests were two-sided, and significance was set at P < 0.05, and 95% confidence intervals were reported. The manuscript was prepared following the STROBE recommendations for an observational case-control study.

Results

Participants

About 305 pregnant women in their second and third trimesters of pregnancy were potentially eligible for the study. However, 175 women were examined for eligibility, and 161 women were confirmed eligible. A total of 155 women were finally included in the study because six women declined periodontal examination. There was no follow-up in this study, and all 155 were included in the final analysis.

Socio-demographic, anthropometric, obstetric, and clinical characteristics of the study sample

The results showed that there were no significant differences in the distribution of age, gestational age, weight during pregnancy, standing height, and the body mass index between pregnant women diagnosed with preeclampsia and normotensive pregnancies (Table 1). From Table 2, it was observed that the employment status (ꭕ2=6.798, P=0.033) and the family history of hypertension (ꭕ2=5.383, P=0.021) were significantly different between the preeclampsia and normotensive pregnancy groups.

Table 1.

The anthropometric and obstetric characteristics of the study sample

Variable	PE	Controls	P-value
Age (years)	30.5±5.2	30.7±5.2	0.781
Gestational age (weeks)	31.0±5.1	30.5±5.5	0.648
Pregnancy weight (Kg)	77.2±14.9	75.1±11.55	0.326
Height (cm)	162.9±5.6	164.4±7.7	0.219
BMI (Kg/m2)	29.0±4.9	27.8±4.3	0.127

Results are summarised as mean (standard deviation).

Table 2.

Socio-demographic, obstetric and clinical characteristics of the study sample

Variable	Categories	PE	Controls	ꭕ2	P-value
Ethnicity	Mole-Dogomba	51(98.1)	94(91.3)	2.659	0.166
Ethnicity	Others	1(1.9)	9(8.7)	2.659	0.166
Religion	Islam	44(84.6)	81(78.6)	0.790	0.519
Religion	Christianity	8(15.4)	22(21.4)	0.790	0.519
Marital Status	Married	51(98.1)	102(99.0)	0.246	>0.99
Marital Status	Single	1(1.9)	1(1.0)	0.246	>0.99
Education Level	None	8(15.4)	14(13.6)	1.703	0.636
	Basic	12(23.1)	26(25.2)
	Secondary	17(32.7)	25(24.3)
	Tertiary	15(28.8)	38(36.9)
Employment Status	Unemployed	8(15.4)	5(4.9)	6.798	0.033
	Self-employed	33(63.5)	62(60.2)
	Salary	11(21.2)	36(35.0)
Previous C/S	No	43(82.7)	85(82.5)	0.001	>0.99
Previous C/S	Yes	9(17.3)	18(17.5)	0.001	>0.99
Alcohol Use During Pregnancy	No	52(100)	102(99.0)	0.508	>0.99
Alcohol Use During Pregnancy	Yes	0(0.0)	1(1.0)	0.508	>0.99
Family History of Hypertension	No	51(98.1)	89(86.4)	5.383	0.021
Family History of Hypertension	Yes	1(1.9)	14(13.6)	5.383	0.021
Family History - Diabetes	No	52(100)	96(93.2)	3.701	0.096
Family History - Diabetes	Yes	0(0.0)	7(6.8)	3.701	0.096
Parity	Nulliparity	10(19.2)	18(17.5)	0.114	0.944
Parity	Primiparity	16(30.8)	34(33.0)
Gravidity	Multiparity	26(50.0)	51(49.5)
	Primigravida	7(13.5)	11(10.7)	0.261	0.605
	Multi-gravida	45(86.5)	92(89.3)	0.261	0.605

Results are summarised as frequency (per cent).

Association between preeclampsia and periodontitis

Periodontal examination of the study sample revealed that the median values of probing pocket depth (PPD), clinical attachment loss (CAL), and plaque index (PI) were significantly higher among pregnant women diagnosed with preeclampsia than among those with normotensive pregnancies (Table 3). Association analyses revealed [adjusted odds ratio (95%CI)] that cleaning of teeth and oral cavity twice daily was protective against preeclampsia, even after controlling for covariates [0.434(0.197-0.956)]. In addition, pregnant women who bled on probing [3.238(1.482-7.075)], were found to have periodontal disease [3.079(1.414-6.704)] or periodontitis [8.905(3.574-22.188)], were more likely to be diagnosed with preeclampsia (Table 4).

Table 3.

Comparing the probing pocket depth (PPD), clinical attachment loss (CAL) and plaque index (PI) between preeclampsia and controls

Variables	PE	Control	P-value
PPD (mm)	4.0(2.3-4.0)	2.0(1.0-3.0)	<0.001
CAL (mm)	5.0(0.0-5.0)	0.0(0.0-0.0)	<0.001
PI	3.0(2.0-3.0)	2.0(1.0-3.0)	<0.001

Results are summarised as median (IQR). PPD: probing pocket depth, CAL: clinical attachment loss, PI: plaque index.

Table 4.

Prevalence of oral cleaning habits and periodontal diseases between preeclampsia and controls

Variables	Category	PE	Control	OR (95%CI)	P-value	AOR (95%CI)*	P-value
Tooth Cleaning (daily)	Once	22(42.3)	27(26.2)			1
Tooth Cleaning (daily)	Twice	30(57.7)	76(73.8)	0.484(0.24-0.979)	0.044	0.434(0.197-0.956)	0.038
Tooth Cleaning Method	Toothbrush	45(86.5)	93(90.3)			1
Tooth Cleaning Method	Toothbrush & Stick	7(13.5)	10(9.7)	1.447(0.517-4.050)	0.482	1.271(0.442-3.654)	0.657
Interdental Cleaning	No	33(63.5)	99(96.1)			1
Interdental Cleaning	Yes	19(36.5)	4(3.9)	14.25(4.521-44.911)	<0.001	17.214(4.564-64.922)	<0.001
Bleeding on Probing	No	14(26.9)	55(53.4)			1
Bleeding on Probing	Yes	38(73.1)	48(46.6)	3.110(1.507-6.420)	0.002	3.238(1.482-7.075)	0.003
Periodontal Disease	No	14(26.9)	53(51.5)			1
Periodontal Disease	Yes	38(73.1)	50(48.5)	2.877(1.394-5.937)	0.004	3.079(1.414-6.704)	0.005
Periodontal Disease	No	14(26.9)	53(51.5)			1
	Periodontitis	34(65.4)	15(14.6)	8.581(3.682-19.999)	<0.001	8.905(3.574-22.188)	<0.001
	Others PD	4(7.7)	35(34.0)	0.433(0.132-1.423)	0.168	0.500(0.146-1.707)	0.269

Results are summarised as frequency (per cent). *Adjusted for employment status and family history of hypertension.

Variations in lipid variables in preeclampsia and periodontitis

From Table 5, the fasting plasma total cholesterol, LDL, VLDL, triglycerides, non-HDL cholesterol, the total cholesterol/HDL, and the LDL/HDL ratios were all higher in preeclampsia than in the controls. However, the fasting plasma HDL cholesterol was lower in preeclampsia than in the controls. Fasting plasma lipid levels were compared in pregnant women with and without periodontal disease separately for the cases and controls (Table 6). It was observed among preeclampsia subjects that the total cholesterol, LDL, non-HDL cholesterol, the total cholesterol/HDL and the LDL/HDL ratios were higher among pregnant women with co-morbidity of preeclampsia and periodontitis than those with only preeclampsia. However, no significant differences in the fasting lipids were observed between normotensive pregnant women with and without periodontitis.

Table 5.

Variations in fasting lipids between preeclampsia and controls

Variables	PE	Control	P-value
TCHOL (mmol/L)	6.0±1.4	4.9±1.1	<0.001
HDL (mmol/L)	1.3±0.3	1.8±0.5	<0.001
LDL (mmol/L)	4.0±1.2	2.6±0.9	<0.001
VLDL (mmol/L)	0.7±0.2	0.5±0.2	<0.001
TRIG (mmol/L)	1.5±0.4	1.1±0.4	<0.001
Non-HDL (mmol/L)	4.6±1.3	3.1±1.0	<0.001
TCHOL/HDL	4.6±1.0	2.8±0.9	<0.001
LDL/HDL	3.0±0.9	1.5±0.7	<0.001

Results are summarised as mean (standard deviation).

Table 6.

Variations in fasting lipids between pregnant women with and without periodontal disease

Variables	PE				Controls
Variables	Healthy	Periodontitis	Other PD	P-value	Healthy	Periodontitis	Other PD	P-value
TCHOL (mmol/L)	4.9±0.7	6.4±1.4*	6.0±1.4	0.002	5.0±1.1	4.6±1.5	4.8±1.0	0.394
HDL (mmol/L)	1.3±0.2	1.3±0.3	1.4±.3	0.707	1.9±0.4	1.6±0.4	1.7±0.5	0.237
LDL (mmol/L)	3.0±0.7	4.4±1.2**	3.8±1.0	0.001	2.6±0.8	2.5±1.1	2.5±1.0	0.905
VLDL (mmol/L)	0.6±0.2	0.7±0.2	0.7±0.2	0.618	0.6±0.3	0.5±0.2	0.5±0.2	0.500
TRIG (mmol/L)	1.4±0.4	1.5±0.4	1.6±0.5	0.621	1.2±0.4	1.0±0.4	1.1±0.4	0.151
Non-HDL (mmol/L)	3.6±0.8	5.1±1.3*	4.6±1.3	0.002	3.2±0.9	3.0±1.3	3.0±0.9	0.739
TCHOL/HDL	3.9±0.7	4.9±1.0*	4.3±0.6	0.005	2.8±0.6	2.9±0.9	2.9±1.1	0.719
LDL/HDL	2.4±0.6	3.3±0.9*	2.8±0.5	0.002	1.5±0.5	1.6±0.9	1.5±0.7	0.617

Results are summarised as mean (standard deviation). *P<0.010, **P<0.001 compared to healthy group.

Interactions between preeclampsia and periodontitis on fasting lipid variables

Linear regression models, fitted with two-way interaction terms, were used to determine whether the combined effect of preeclampsia and periodontal diseases or periodontitis on lipid variables was more or less than the sum of their separate effects, adjusting for covariates. From Table 7, the effects of both preeclampsia and periodontal disease on total cholesterol are not significant; however, their combined effect accounted for a 1.737 mmol/L increase in total cholesterol [B=1.737 (95%CI: 0.891-2.583)]. Similar interactions between preeclampsia and periodontal disease have been observed on LDL, non-HDL, total cholesterol/HDL ratio, and the LDL/HDL ratio. The same can be observed between preeclampsia and periodontitis (Table 8). The test of assumptions data for multivariable linear regression can be found in the supplementary Tables S1-S10 and supplementary Figures S1-S10.

Table 7.

Interactions between preeclampsia and periodontal diseases on fasting lipid variables

Dependent variables	Independents variables	B	95.0% CI for B		P-value
Dependent variables	Independents variables		Lower bound	Upper bound
TCHOL (mmol/L)	(Constant)	4.737	4.206	5.268	<0.001
	Employment Status	0.144	-0.179	0.466	0.380
	Family History - Hypertension	0.641	0.010	1.272	0.047
	Preeclampsia (PE)	-0.001	-0.692	0.690	0.998
	Periodontal Disease (PD)	-0.287	-0.737	0.163	0.209
	PE*PD	1.737	0.891	2.583	<0.001
HDL (mmol/L)	(Constant)	1.757	1.573	1.940	<0.001
	Employment Status	0.063	-0.049	0.174	0.269
	Family History - Hypertension	0.094	-0.124	0.312	0.397
	Preeclampsia (PE)	-0.555	-0.794	-0.316	<0.001
	Periodontal Disease (PD)	-0.137	-0.292	0.019	0.084
	PE*PD	0.211	-0.081	0.504	0.156
LDL (mmol/L)	(Constant)	2.391	1.953	2.829	<0.001
	Employment Status	0.114	-0.152	0.38	0.400
	Family History - Hypertension	0.412	-0.109	0.932	0.120
	Preeclampsia (PE)	0.456	-0.115	1.026	0.116
	Periodontal Disease (PD)	-0.075	-0.446	0.296	0.689
	PE*PD	1.429	0.732	2.127	<0.001
VLDL (mmol/L)	(Constant)	0.529	0.444	0.614	<0.001
	Employment Status	0.003	-0.049	0.055	0.909
	Family History - Hypertension	0.153	0.052	0.254	0.003
	Preeclampsia (PE)	0.116	0.005	0.227	0.041
	Periodontal Disease (PD)	-0.042	-0.114	0.03	0.253
	PE*PD	0.091	-0.045	0.227	0.187
TRIG (mmol/L)	(Constant)	1.158	0.984	1.332	<0.001
	Employment Status	-0.01	-0.116	0.095	0.846
	Family History - Hypertension	0.224	0.018	0.431	0.034
	Preeclampsia (PE)	0.281	0.055	0.507	0.015
	Periodontal Disease (PD)	-0.084	-0.231	0.064	0.264
	PE*PD	0.19	-0.087	0.466	0.178
non-HDL (mmol/L)	(Constant)	2.98	2.497	3.464	<0.001
	Employment Status	0.081	-0.212	0.375	0.586
	Family History - Hypertension	0.547	-0.028	1.122	0.062
	Preeclampsia (PE)	0.554	-0.075	1.183	0.084
	Periodontal Disease (PD)	-0.15	-0.560	0.259	0.470
	PE*PD	1.526	0.756	2.296	<0.001
TCHOL/HDL	(Constant)	2.725	2.321	3.129	<0.001
	Employment Status	0.02	-0.225	0.265	0.872
	Family History - Hypertension	0.243	-0.237	0.723	0.319
	Preeclampsia (PE)	1.134	0.608	1.66	<0.001
	Periodontal Disease (PD)	0.128	-0.214	0.471	0.460
	PE*PD	0.788	0.144	1.432	0.017
LDL/HDL	(Constant)	1.405	1.057	1.753	<0.001
	Employment Status	0.031	-0.181	0.242	0.776
	Family History - Hypertension	0.174	-0.24	0.587	0.408
	Preeclampsia (PE)	0.928	0.475	1.381	<0.001
	Periodontal Disease (PD)	0.134	-0.161	0.429	0.370
	PE*PD	0.773	0.218	1.327	0.007

Table 8.

Interactions between preeclampsia and periodontitis on fasting lipid variables

Dependent variables	Independent variables	B	95.0% CI for B		P-value
Dependent variables	Independent variables		Lower bound	Upper bound
TCHOL (mmol/L)	(Constant)	4.605	4.006	5.205	<0.001
	Employment Status	0.187	-0.184	0.558	0.319
	Family History - Hypertension	1.209	0.385	2.034	0.004
	Preeclampsia (PE)	0.078	-0.626	0.782	0.827
	Periodontitis	-0.319	-0.996	0.359	0.354
	PE*Periodontitis	1.811	0.809	2.813	0.001
HDL (mmol/L)	(Constant)	1.724	1.535	1.913	<0.001
	Employment Status	0.083	-0.034	0.200	0.162
	Family History - Hypertension	0.140	-0.120	0.400	0.288
	Preeclampsia (PE)	-0.547	-0.769	-0.325	<0.001
	Periodontitis	-0.200	-0.414	0.013	0.065
	PE*Periodontitis	0.276	-0.040	0.591	0.086
LDL (mmol/L)	(Constant)	2.322	1.838	2.806	<0.001
	Employment Status	0.126	-0.174	0.425	0.407
	Family History - Hypertension	0.818	0.152	1.484	0.017
	Preeclampsia (PE)	0.510	-0.058	1.079	0.078
	Periodontitis	-0.048	-0.595	0.500	0.863
	PE*Periodontitis	1.451	0.642	2.261	0.001
VLDL (mmol/L)	(Constant)	0.517	0.422	0.612	<0.001
	Employment Status	0.001	-0.058	0.060	0.973
	Family History - Hypertension	0.263	0.132	0.395	<0.001
	Preeclampsia (PE)	0.130	0.018	0.242	0.023
	Periodontitis	-0.046	-0.154	0.062	0.400
	PE*Periodontitis	0.088	-0.071	0.247	0.277
TRIG (mmol/L)	(Constant)	1.169	0.979	1.360	<0.001
	Employment Status	-0.033	-0.151	0.084	0.575
	Family History - Hypertension	0.368	0.106	0.630	0.006
	Preeclampsia (PE)	0.298	0.074	0.521	0.010
	Periodontitis	-0.189	-0.405	0.026	0.084
	PE*Periodontitis	0.278	-0.041	0.596	0.087
non-HDL (mmol/L)	(Constant)	2.881	2.333	3.429	<0.001
	Employment Status	0.104	-0.235	0.443	0.543
	Family History - Hypertension	1.070	0.316	1.823	0.006
	Preeclampsia (PE)	0.625	-0.018	1.268	0.057
	Periodontitis	-0.118	-0.737	0.501	0.707
	PE*Periodontitis	1.535	0.619	2.451	0.001
TCHOL/HDL	(Constant)	2.697	2.286	3.107	<0.001
	Employment Status	0.007	-0.247	0.261	0.955
	Family History - Hypertension	0.585	0.020	1.149	0.042
	Preeclampsia (PE)	1.178	0.696	1.660	<0.001
	Periodontitis	0.118	-0.346	0.582	0.615
	PE*Periodontitis	0.841	0.155	1.527	0.017
LDL/HDL	(Constant)	1.373	1.016	1.730	<0.001
	Employment Status	0.027	-0.194	0.248	0.811
	Family History - Hypertension	0.452	-0.039	0.944	0.071
	Preeclampsia (PE)	0.965	0.545	1.384	<0.001
	Periodontitis	0.124	-0.280	0.528	0.545
	PE*Periodontitis	0.830	0.233	1.427	0.007

Discussion

The study aimed to investigate the relationship between preeclampsia and periodontitis on fasting plasma lipid levels. The women diagnosed with preeclampsia were not significantly different from the controls in chronological age, gestational age and body mass index. It was observed that preeclampsia was significantly associated with periodontitis. Sub-group analysis showed that the total cholesterol, LDL, non-HDL, total cholesterol/HDL, and LDL/HDL were higher in preeclamptic women with periodontitis than in those without periodontitis. However, there were no significant differences in lipid variables between normotensive pregnant women with and without preeclampsia. It was also observed that significant interactions between preeclampsia and periodontitis or periodontal disease occurred on fasting plasma lipid variables.

The current study supports growing evidence that maternal periodontitis is associated with preeclampsia, one of the major causes of maternal and perinatal morbidity and mortality. Previous observational studies and meta-analyses have demonstrated that women with periodontal disease, including periodontitis, are approximately two to four times more likely to develop preeclampsia compared with their periodontally healthy counterparts.^23,24 This positive association may suggest that chronic oral inflammation may contribute to systemic vascular and immune disturbances that characterise preeclampsia.

The observed association between preeclampsia and periodontitis have biological plausibility. It has been observed that periodontal pathogens, such as Fusobacterium nucleatum and Porphyromonas gingivalis, can translocate into the systemic circulation, leading to endothelial dysfunction and a maternal inflammatory response.^25,26 These mechanisms parallel the pathophysiology of preeclampsia, which is characterised by exaggerated inflammatory and oxidative stress responses, endothelial activation and abnormal placentation. High levels of inflammatory mediators, including cytokines such as tumour necrosis factor-alpha, interleukin-6, and C-reactive protein, in women with periodontal disease may amplify endothelial injury and placental ischemia, predisposing to hypertensive complications during pregnancy.^27,28 Although observational studies consistently show a positive relationship, causality remains uncertain due to heterogeneity in diagnostic criteria for periodontitis, study design and potential residual confounding by socioeconomic status, obesity, smoking and chronic diseases.^23,29 In addition, previous randomised controlled trials of periodontal therapy during pregnancy have demonstrated improvements in oral health but have not consistently reduced the incidence of preeclampsia or other adverse pregnancy outcomes.¹² This observation may be due to the late timing of intervention or the irreversible nature of placental alterations once preeclampsia is established. However, maintaining periodontal health remains vital during pregnancy, as treatment is safe and may reduce systemic inflammation.³⁰

Disparity in fasting lipids between pregnant women with and without periodontitis was only observed among the preeclampsia group, but not the controls. This demonstrates a distinct dysregulated lipid profile among preeclamptic women, which is made worse by the presence of periodontitis. This suggests a potential synergistic interaction between the two conditions, as was observed in the study.³¹ The absence of marked differences in lipid variables between normotensive pregnant women with and without periodontitis indicates that periodontal inflammation alone may not be sufficient to disrupt lipid metabolism in healthy pregnancies.³² This observation reinforces the concept that periodontitis may act as an effect modifier, which amplifies pre-existing conditions characterised by metabolic disturbances such as preeclampsia, rather than acting as an independent risk factor.³³

This study found significant interactions between preeclampsia and periodontitis on fasting plasma lipid levels. This may indicate that the coexistence of both conditions may synergistically worsen maternal lipid metabolism during pregnancy.²³ This finding supports the growing body of evidence associating both periodontitis and preeclampsia with oxidative stress, systemic inflammation, and endothelial dysfunction, which are known to impact lipid homeostasis.⁷ Preeclampsia is marked by perturbed lipid metabolism, commonly manifesting as elevated total cholesterol, low-density lipoprotein and triglycerides levels, along with decreased high-density lipoprotein concentrations.³⁴ Similarly, chronic periodontitis has been associated with dysregulated lipid metabolism, potentially due to systemic dissemination of inflammatory cytokines and bacterial endotoxins such as lipopolysaccharides that stimulate hepatic lipid synthesis.¹⁷ The observed interaction suggests that inflammatory mediators derived from periodontal infection may worsen the lipid abnormalities typically seen in preeclampsia, amplifying the risk of vascular dysfunction. This synergistic effect between preeclampsia and periodontitis could be mediated by overlapping pathophysiological pathways of the disease conditions. Periodontal pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum can invade the bloodstream, activating toll-like receptors and triggering the release of pro-inflammatory cytokines such as IL-6, TNF-α, and CRP.³⁵ These cytokines not only contribute to endothelial injury but also impair lipid transport and oxidation, which may lead to hyperlipidemia and oxidative modification of LDL particles. In preeclamptic women with concurrent periodontal disease, this compounded inflammatory burden may promote greater vascular lipid deposition and endothelial activation, consistent with our finding of elevated plasma lipid levels in those with both conditions.³⁶ Although causality cannot be inferred, the significant interaction between preeclampsia and periodontitis on lipid levels underscores the potential cardiometabolic link between oral and systemic health.³⁷

This study contributes vital baseline data regarding the link between oral and systemic health that is scarce or non-existent in the Ghanaian population. In addition, previous studies were largely association studies, which did not establish the possible synergistic effect between preeclampsia and periodontitis on cardiometabolic factors. However, causality could not be inferred due to the case-control design of the study. It was also not possible to determine changes in fasting lipid levels since the study was not longitudinal in design.

Conclusion

The study found that preeclampsia is associated with periodontal diseases, particularly periodontitis. In addition, there is an interaction between preeclampsia and periodontitis of cardiometabolic risk factors in pregnancy. These results highlight the need for an integrated antenatal care that includes periodontal screening and management, particularly in women at high risk for preeclampsia.

Supplemental material

Supplemental material - Preeclampsia, periodontitis and their interactions on cardiometabolic risk markers in pregnancy: A case-control study

Supplemental material for Preeclampsia, periodontitis and their interactions on cardiometabolic risk markers in pregnancy: A case-control study by Richard Ayimbire, Moses Banyeh, Gabriel Abbam, Laud Anthony W. Basing, Shafiat Omotoyosi Shittu, Michael Antunmuni Yelibora, David Ayim Antwi, Munkaila Adam, Issah Zabsonre Alhassan in Journal of Public Health Research

Footnotes

Acknowledgements

The researchers wish to acknowledge the Institute for Interdisciplinary Studies (IIR) of the University for Development Studies for facilitating the funding process of the study. In addition, Dr Jonathan Adongo Akeleyigna, Dr Asoma Awudu and Dr Nimat’ullah Obeitor, of the Dental, Eye, Ear, Nose and Throat (DEENT) sub-BMC and the staff of the Antenatal Clinic of the Tamale Teaching Hospital are acknowledged for granting the researchers access to the clinic and clients to enable us to obtain data for the study.

ORCID iDs

Moses Banyeh

Issah Zabsonre Alhassan

Ethical considerations

The study was approved by the institutional review board of the University for Development (Ref#: UDS/RB/0085/25). Permission to undertake the study was obtained from the Tamale Teaching Hospital. The study complied with the recommendations of the 1964 Declaration of Helsinki and its later amendments regarding human subject studies. Participation was voluntary, and confidentiality of all data was maintained. Pregnant women diagnosed with preeclampsia received prompt obstetric care according to national guidelines, and those who were diagnosed with periodontitis were referred for appropriate periodontal management.

Consent to participate

Written informed consent was obtained from all participants.

Consent for publication

The participants gave consent to publish the findings of the study.

Author contribution

RA, MB, GA, LAWB, SOS, IZA-Conceptualisation, methodology; RA, MAY, DAA, MA-experimentation, data collection; RA, MB- data analysis and interpretation, writing-draft; All authors have read and approved the final version of the manuscript. The corresponding author had full access to all of the data in this study, and he takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the University for Development Studies Research Fund (Ref#: CALL 24-1).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data supporting the findings of the current study are available from the corresponding author upon reasonable request.*

Supplemental material

Supplemental material for this article is available online.

References

Facca

Famá

EAB

Mastroianni-Kirsztajn

, et al.

Why Is Preeclampsia still an Important Cause of Maternal Mortality Worldwide?

Rev Bras Ginecol Obstet 2020; 42: 586–587, 20200929. https://doi.org/10.1055/s-0040-1714132

Fox

Kitt

Leeson

, et al. Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J Clin Med 2019; 8: 20191004. https://doi.org/10.3390/jcm8101625

Dakal

Xiao

Bhusal

, et al. Lipids dysregulation in diseases: core concepts, targets and treatment strategies. Lipids Health Dis 2025; 24: 61: 20250221. https://doi.org/10.1186/s12944-024-02425-1

Fantone

Ermini

Piani

, et al. Downregulation of argininosuccinate synthase 1 (ASS1) is associated with hypoxia in placental development. Hum Cell 2023; 36: 1190–1198. 20230330. DOI: https://doi.org/10.1007/s13577-023-00901-x

Marzioni

Piani

Di Simone

, et al. Importance of STAT3 signaling in preeclampsia. Int J Mol Med 2025; 55: 20250207, (Review). https://doi.org/10.3892/ijmm.2025.5499

Könönen

Gursoy

. Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues. J Clin Med 2019; 8: 20190731. https://doi.org/10.3390/jcm8081135

Martínez-García

Hernández-Lemus

. Periodontal Inflammation and Systemic Diseases: An Overview. Front Physiol 2021; 12: 709438–20211027. DOI: https://doi.org/10.3389/fphys.2021.709438

Bui

Almeida-da-Silva

CLC

Huynh

, et al. Association between periodontal pathogens and systemic disease. Biomedical journal 2019; 42: 27–35. https://doi.org/10.1016/j.bj.2018.12.001

Tattar

da Costa

BDC

Neves

VCM

. The interrelationship between periodontal disease and systemic health. British Dental Journal 2025; 239: 103–108. https://doi.org/10.1038/s41415-025-8642-2

10.

Tang

Chen

. Association between periodontitis and adverse pregnancy outcomes: two-sample Mendelian randomisation study. International Dental Journal 2024; 74: 1397–1404. https://doi.org/10.1016/j.identj.2024.05.001

11.

Chen

Yang

, et al. Maternal periodontitis may cause lower birth weight in children: genetic evidence from a comprehensive Mendelian randomization study on periodontitis and pregnancy. Clin Oral Investig 2024; 28: 194–20240305. https://doi.org/10.1007/s00784-024-05591-9

12.

Anas

Sultan

Fazal

, et al. Impact of periodontal therapy on adverse pregnancy outcomes: a systematic review of randomized controlled trials. Periodontal and Implant Research 2025; 9: 17. https://doi.org/10.1007/s41894-025-00161-y

13.

Newnham

Ball

, et al. Treatment of periodontal disease during pregnancy: a randomized controlled trial. Obstet Gynecol 2009; 114: 1239–1248. https://doi.org/10.1097/AOG.0b013e3181c15b40

14.

Boah

Abanga

Adokiya

. Quality of antenatal care services received by women of reproductive age prior to delivery in selected public health facilities in the northern zone of Ghana. BMC Health Services Research 2024; 24: 1063. https://doi.org/10.1186/s12913-024-11491-1

15.

Hewlett

Anto

Blankson

, et al. Periodontitis prevalence and severity in an African population: A cross-sectional study in the Greater Accra Region of Ghana. J Periodontol 2022; 93: 732–744. 20220103. DOI: https://doi.org/10.1002/jper.21-0329

16.

Hewlett

Blankson

Aheto

JMK

, et al. Assessment of oral health status in a Ghanaian population: rationale, methods, and population characteristics. BMC Oral Health 2022; 22: 67–20220312. https://doi.org/10.1186/s12903-022-02090-9

17.

Zhao

, et al. Association between periodontitis and blood lipid levels: a cross-sectional study. BMC Oral Health 2025; 25: 1055. https://doi.org/10.1186/s12903-025-06341-3

18.

Uwambaye

Kerr

Rulisa

, et al. Prevalence of periodontitis and associated factors among pregnant women: a cross sectional survey in Southern Province, Rwanda. Rwanda Journal of Medicine and Health Sciences 2021; 4: 131–150. https://doi.org/10.4314/rjmhs.v4i1.10

19.

Hess

Gilill

DembÃ

. Prevalence and predictors of periodontal disease among pregnant women in Mali, West Africa. Ann Med Health Sci Res 2017; 7: 263.

20.

Q-A

Akhter

Coulton

, et al. Periodontitis and preeclampsia in pregnancy: A systematic review and meta-analysis. Maternal and Child Health Journal 2022; 26: 2419–2443. https://doi.org/10.1007/s10995-022-03556-6

21.

Moussa

Rajapreyar

. ACOG Practice Bulletin No. 212: pregnancy and heart disease. Obstetrics & Gynecology 2019; 134: 881–882. https://doi.org/10.1097/AOG.0000000000003497

22.

Armitage

Wang

, et al. Low prevalence of a periodontitis‐associated interleukin‐1 composite genotype in individuals of Chinese heritage. Journal of Periodontology 2000; 71: 164–171. https://doi.org/10.1902/jop.2000.71.2.164

23.

Akhter

Coulton

, et al. Periodontitis and Preeclampsia in Pregnancy: A Systematic Review and Meta-Analysis. Matern Child Health J 2022; 26: 2419–2443. 20221008. DOI: https://doi.org/10.1007/s10995-022-03556-6

24.

Karimi

Samiee

Moradi

. The association between periodontal disease and risk of adverse maternal or neonatal outcomes: A systematic review and meta-analysis of analytical observational studies. Health Sci Rep 2023; 6: e1630–20231019. DOI: https://doi.org/10.1002/hsr2.1630

25.

Cao

Liu

, et al. Association Between Periodontitis and Preeclampsia: A Bidirectional Mendelian Randomisation Analysis. Int Dent J 2024; 74: 1438–1446. 20240608. DOI: https://doi.org/10.1016/j.identj.2024.05.004

26.

Ganesh

Mangaiyarkarasi

Anagol

. Significant association between maternal periodontitis and pre-eclampsia complications - A retrospective case control study. J Indian Soc Periodontol 2025; 29: 123–129. 20250819. DOI: https://doi.org/10.4103/jisp.jisp_85_24

27.

Kany

Vollrath

Relja

. Cytokines in Inflammatory Disease. Int J Mol Sci 2019; 20: 20191128. https://doi.org/10.3390/ijms20236008

28.

Bhol

Bhanjadeo

Singh

, et al. The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomedicine & Pharmacotherapy 2024; 178: 117177. https://doi.org/10.1016/j.biopha.2024.117177

29.

Kim

. Inferring causality from observational studies: the role of instrumental variable analysis. Kidney International 2021; 99: 1303–1308. https://doi.org/10.1016/j.kint.2021.03.018

30.

Bostanci

. Periodontal health and pregnancy outcomes: Time to deliver. Acta Obstet Gynecol Scand 2023; 102: 648–651. https://doi.org/10.1111/aogs.14548

31.

Zhao

Yang

Zhu

, et al. Multiomics Analysis Reveals Significant Disparities in the Oral Microbiota and Metabolites Between Pregnant Women with and without Periodontitis. Infect Drug Resist 2024; 17: 4665–4683. 20241025. DOI: https://doi.org/10.2147/idr.S475164

32.

Oyeniran

Changkat

Mohammed

, et al. A Comparative Study of Serum Lipid Levels in Pregnant Normotensive and Pre-eclamptic Women in Dalhatu Araf Specialist Hospital Lafia, Nigeria. Niger Med J 2023; 64: 33–42. 20230505.

33.

Spradley

Palei

Granger

. Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2015; 309: R1326–R1343. https://doi.org/10.1152/ajpregu.00178.2015

34.

Stadler

Scharnagl

Wadsack

, et al. Preeclampsia Affects Lipid Metabolism and HDL Function in Mothers and Their Offspring. Antioxidants (Basel) 2023; 12: 20230324. https://doi.org/10.3390/antiox12040795

35.

Hajishengallis

Chavakis

. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nature Reviews Immunology 2021; 21: 426–440. https://doi.org/10.1038/s41577-020-00488-6

36.

Zhang

. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 2008; 103: 398–406. 20080703. DOI: https://doi.org/10.1007/s00395-008-0733-0

37.

Ruan

Wang

Ying

, et al. Bioinformatics analysis of shared biomarkers and immune pathways of preeclampsia and periodontitis. BMC Pregnancy and Childbirth 2025; 25: 217. https://doi.org/10.1186/s12884-025-07277-w

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