The Effect of Vitamin D Supplementation on Fetal Cerebroplacental Ratio in Pregnant Women with Systemic Lupus Erythematosus: A Quasi-Experimental Study

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Title Page

Nurul Islamy^1*, Setyorini Irianti¹, Muhammad Alamsyah Aziz¹, Sumartini Dewi², Annisa Dewi Nugrahani^1,3, Amillia Siddiq¹, Anita Deborah Anwar¹, Budi Handono¹, Jusuf Sulaeman Effendi¹

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

²Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

³Doctoral Program, Faculty of Medicine, Universitas Padjadjaran

Corresponding Author:

Nurul Islamy^1*

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: nurulislamy@gmail.com

List of Authors:

Nurul Islamy^1*

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: nurulislamy@gmail.com

Muhammad Alamsyah Aziz¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: alamsyahaziz9119@gmail.com

Setyorini Irianti¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: setyorini@unpad.ac.id

Sumartini Dewi²

²Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: sumartini.dewi@unpad.ac.id.

Annisa Dewi Nugrahani¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

³Doctoral Program, Faculty of Medicine, Universitas Padjadjaran

Email: annisa16005@mail.unpad.ac.id

Amillia Siddiq¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: amel2000id@yahoo.com

Anita Deborah Anwar¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: anitadebbya@yahoo.com

Budi Handono¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: budihandono9@yahoo.com

Jusuf Sulaeman Effendi¹

¹Maternal Fetal Medicine Division of Department of Obstetrics and Gynecology,

Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

Email: jusufse@yahoo.com

The Effect of Vitamin D Supplementation on Fetal Cerebroplacental Ratio in Pregnant Women with Systemic Lupus Erythematosus: A Quasi-Experimental Study

Abstract

Objective

Pregnancy in women with systemic lupus erythematosus (SLE) carries increased maternal and fetal risks. Vitamin D plays an essential role in placental vascular function and fetal circulation regulation. The cerebroplacental ratio (CPR) reflects fetal adaptation to chronic hypoxia through the brain-sparing effect. This study aimed to evaluate the effect of vitamin D supplementation on fetal CPR in pregnant women with SLE. A quasi-experimental pretest–posttest study was conducted at Dr. Hasan Sadikin General Hospital, Bandung, from May to October 2024. Ten participants received 5000 IU of vitamin D daily for three months. Serum vitamin D and fetal CPR were measured monthly and analyzed using SPSS 24.0.

Results Following supplementation, the mean serum vitamin D increased from 21.92 ± 4.85 ng/mL to 35.85 ± 5.68 ng/mL (p = 0.05), with hypovitaminosis resolved in all subjects (p = 0.004). The mean CPR improved from 1.30 ± 0.16 in month 1 to 1.61 ± 0.24 in month 2 and remained stable in month 3 (p < 0.0001). Thus, three months of 5000 IU vitamin D supplementation in pregnant women with systemic lupus erythematosus (SLE) leads to a noticeable change in vitamin D levels and fetal cerebroplacental ratio (CPR), but the effect on CPR shows a weak, non-significant correlation.

Keywords:

Vitamin D

systemic lupus erythematosus

cerebroplacental ratio

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that predominantly affects women of reproductive age, characterized by chronic inflammation and immune dysfunction [1]. Global prevalence rates range from 15.87 to 108.92 cases per 100,000 individuals, with an annual incidence of 5.14 new cases per 100,000. In Indonesia, there has been an increase in SLE patient visits, with a significant rise from 17.9% to 58% [2–4]. Pregnancy in women with SLE is considered high-risk due to potential complications for both the mother and fetus. Studies show that maternal mortality is significantly higher, and adverse pregnancy outcomes, such as preeclampsia and fetal distress, are common. Fetal complications, including increased rates of stillbirth and premature birth, are also more frequent in women with SLE [5–11].

Vitamin D plays a crucial role in immune modulation, bone formation, and vascular regulation. Its circulating form, 25-hydroxycholecalciferol, reflects the body's vitamin D status. Supplementation is often necessary to achieve optimal blood levels, with the safe upper daily limit set at 4,000 IU by the Institute of Medicine [12, 13]. Studies indicate that vitamin D supplementation during pregnancy is effective, with doses ranging from 2,000 to 4,000 IU per day deemed safe. Vitamin D deficiency is linked to heightened disease activity in SLE patients and contributes to complications such as immune dysregulation. Factors such as inadequate sun exposure, diet, and corticosteroid use can exacerbate vitamin D deficiency in SLE patients [12–14].

The role of vitamin D in regulating placental blood flow and fetal development is also significant. Vitamin D supplementation has been shown to improve blood vessel volume in the maternal-fetal circulation, promoting better blood flow to the fetus. Studies have also demonstrated that vitamin D influences angiogenesis in the placenta, enhancing the formation of capillary structures and improving blood flow [15–17]. Research on rats has indicated that vitamin D deficiency leads to reduced blood vessel size and impaired capillary growth in the placenta. This effect could play a vital role in improving placental function and reducing the risks of fetal growth restriction and other complications in SLE pregnancies [2, 6].

The cerebroplacental ratio (CPR) is a key diagnostic tool for assessing fetal blood flow and placental insufficiency [20–27]. It measures the ratio of blood flow between the fetal middle cerebral artery and the umbilical artery, with values greater than 1.08 considered normal. Low CPR is associated with adverse outcomes, such as abnormal fetal growth and increased fetal mortality. Vitamin D supplementation has shown potential in improving CPR, particularly in cases of early fetal growth restriction [27–31]. This study aims to explore the effects of vitamin D supplementation on CPR in pregnant women with SLE, measuring maternal vitamin D levels and CPR values before and after supplementation to assess its impact on pregnancy outcomes.

Materials and Methods

Study Design and Eligibility Criteria

A quasi-experimental pretest-posttest study design was conducted on 13 pregnant women with SLE at a tertiary hospital in Bandung, Indonesia. Inclusion criteria included mild disease activity (SLEDAI < 6) and gestational age < 24 weeks. Pregnant women diagnosed with Systemic Lupus Erythematosus (SLE) from the Rheumatology Clinic at a tertiary hospital in West Java (diagnostic criteria according to SLICC 2012 or EULAR 2018) with disease activity in remission or low (SLEPDAI score of 0–5); Subjects aged between 18 and 40 years [27]. Pregnant women between 20 and 25 weeks of gestation, based on the last menstrual period (LMP) or ultrasound, singleton pregnancy, and patients who had written consent to participate in the study were included in this study. Nevertheless, pregnant women receiving medications that interact with vitamin D (e.g., digoxin, diazepam, verapamil, thiazide, and heparin), fetuses with chromosomal abnormalities or congenital defects patients with with active tuberculosis or undergoing treatment and or liver or kidney dysfunction as well as patients with with hypercalcemia (serum calcium levels > 10.5 mg/dl) were excluded.

Sampling and Laboratory Procedures

Patients who meet the inclusion criteria will sign an informed consent form after receiving thorough and clear explanations about the study. A comprehensive anamnesis will be conducted, gathering personal details such as full name, medical record number, date of birth or age, address, phone number, educational background, occupation, and medical history using a questionnaire. Participants will also be educated on the importance of vitamin D during pregnancy and the research procedures. Vitamin D levels will be assessed through blood sample collection (3–5 ml) from a vein in the arm, followed by analysis using the enzyme-linked immunosorbent assay (ELISA) method (ng/ml) at tertiary hospital (Hasan Sadikin General Hospital) Laboratory.

Calcium levels will be measured before and after vitamin D supplementation, and ultrasonographic assessments, including biometry, gestational age estimation, fetal weight, and pathological abnormalities, will be performed using a Voluson S8 ultrasound machine (GE, USA). Doppler ultrasound will be conducted to measure the middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices (PI) to calculate the cerebroplacental ratio (CPR). Doppler assessments will be performed at baseline, 1 month, 2 months, and 3 months post-supplementation. Vitamin D supplementation of 5000 IU per day will be administered for 3 months, and any adverse effects will be monitored and reported. Side effects such as anorexia, vomiting, constipation, neuropsychiatric manifestations, cardiovascular issues, polyuria, or renal colic will be recorded, with appropriate management provided. If adverse effects are mild, symptomatic treatment will be administered, while severe effects will result in discontinuation of the supplementation and the patient being withdrawn from the study.

The research will take place at the Obstetrics and Gynecology Outpatient Installation at RSUP Dr. Hasan Sadikin, Bandung, from May to October 2024, after obtaining approval from the Ethics Committee.

Statistical Analysis

The analysis conducted aligns with the research problem and the type of data used. For numerical data, a normality test is performed prior to statistical testing, using the Shapiro-Wilk test for datasets with fewer than 50 samples (with the alternative Kolmogorov-Smirnov test employed for datasets larger than 50), to determine whether the data follows a normal distribution. Subsequent statistical analyses are carried out according to the research objectives and hypotheses. To compare characteristics between two paired research groups, a paired T-Test is used if the data is normally distributed, while the Wilcoxon test serves as an alternative for non-normally distributed data. For categorical data, McNemar's test is employed. Correlational analysis for numerical hypotheses uses the Pearson correlation test for normally distributed data, with the Spearman test as an alternative for non-normally distributed data. Statistical significance is determined by the p-value, where p ≤ 0.05 is considered statistically significant, and p > 0.05 is deemed not statistically significant. The data is recorded in a specialized form and subsequently analyzed using SPSS version 24.0 for Windows.

Results

The research subjects were selected after obtaining approval from the Health Research Ethics Committee of Dr. Hasan Sadikin General Hospital, Bandung, under the reference number DP.04.03/D.XIV.6.5/148/2024. Data collection was conducted from May to October 2024, focusing on pregnant women at 20–25 weeks of gestation who had been diagnosed with systemic lupus erythematosus (SLE) at the Rheumatology Clinic of RSHS. Subjects were recruited during outpatient follow-up visits and were required to have disease activity in remission or at a low level (SLEPDAI score of 0–5).

To meet the required sample size, adjustments were made to account for time constraints and the rarity of SLE cases. Consequently, the power test was set at 80%, with a 20% error margin, yielding a minimum sample size of 9 participants. A total of 13 pregnant women meeting the gestational age and SLE criteria were initially included. However, two patients were excluded due to moderate-to-severe SLE activity (SLEPDAI score 6–12) observed during outpatient follow-up at the High-Risk Clinic of RSHS.

The first excluded patient exhibited hematological involvement, with a platelet count of 39,000/mm³, corresponding to moderate SLE activity (SLEPDAI score 6–12). The second excluded patient, at 25 weeks of gestation, displayed renal involvement, characterized by acute kidney injury (AKI) stage 1 (creatinine level 1.12 mg/dL), proteinuria + 4 (437.17 mg/dL), and urinary erythrocytes at 110.2/µL.

Ultimately, 11 patients met the inclusion criteria and received 5000 IU of vitamin D supplementation for three months, with Doppler assessments performed. During the evaluation period, one subject at 20 weeks of gestation was dropped from the study after experiencing vaginal bleeding and intrauterine fetal death within five days of the first follow-up visit (CRP 1.31 mg/dL; leukocyte esterase + 3). This patient had a SLEPDAI score of 2, with musculoskeletal and mucocutaneous involvement. As a result, the final analysis included 10 research subjects.

The characteristics of the research subjects are presented in Table 1. The average age of patients diagnosed with SLE was 28.30 years, with a standard deviation (SD) of 5.165. The age range was 19–35 years, indicating that the majority of patients were in the young adult group. The mean body mass index (BMI) was 20.78, with an SD of 2.522, and a range of 17.29–24.86, suggesting that most patients fell within the normal weight category. The average disease duration among the participants was 3.14 years, with an SD of 2.416 and a range of 0.42–7 years. Regarding gravidity, 3 patients (30%) were primigravida (first-time pregnancies), while 7 patients (70%) were multigravida (previously pregnant).

Table 1
Baseline Subject Characteristics
Variables	(N = 10)
Age (Years)
Mean ± Std	28.30 ± 5.165
Median	28.50
Range (min-max)	19.0–35.00
Body Mass Index/BMI (kg/m²)
Mean ± Std	20.78 ± 2.522
Median	20.995
Range (min-max)	17.29–24.86
SLE Duration
Mean ± Std	3.140 ± 2.416
Median	2.500
Range (min-max)	0.40–7.00
Gravida
Primigravida	3(30%)
Multigravida	7(70%)
*Notes: Categorical data is presented as counts/frequencies and percentages, while numerical data is presented using the mean, median, standard deviation, and range. BMI: Body Mass Index; SLE: Systemic Lupus Erythematosus

Table 2
Comparison of Vitamin D Levels Before and After Supplementation
Variable Vitamin D	Group		P-Value
	Before	After
	N = 10	N = 10
Mean ± Std	21.92 ± 4.852	35.85 ± 5.680	0.005*
Median	21.29	35.24
Range (min-max)	14.13–30.24	30.94–49.68
*Notes: Numerical data P values were tested using the Wilcoxon test for non-normally distributed data. Statistical significance is based on a P value < 0.05.

Among the 10 analyzed participants, Vitamin D levels significantly increased from 21.92 ± 4.85 to 35.85 ± 5.68 nmol/L post-supplementation (P = 0.05) as seen in Table 2. CPR improved from 1.30 ± 0.16 in month 1 to 1.61 ± 0.24 in month 3 (P < 0.0001).

For the analysis of numerical data, a paired t-test was used because the data was normally distributed, including CPR (pre- vs post-1), CPR (pre vs post-2), CPR (pre vs post-3), CPR (post-1 vs post-2), CPR (post-1 vs post-3), and CPR (post-2 vs post-3). The statistical analysis for the above research group revealed P values for the CPR variable smaller than 0.05 (P < 0.05), indicating statistical significance (Table 3). Therefore, it can be explained that there is a statistically significant difference in the mean CPR values between the Pre vs Post-1, Pre vs Post-2, and Pre vs Post-3 groups.

Table 3
Comparison of CPR Pre, Post-1, Post-2, and Post-3 Across Timepoints
Variables	N	CPR			P-Value
Variables	N	Mean ± Std	Median	Range (min-max)	P-Value
Pre	10	1.30 ± 0.159	1.28	1.01–1.54	0.007*
Post-1	10	1.61 ± 0.243	1.55	1.30–2.06
Pre	10	1.30 ± 0.159	1.28	1.01–1.54	0.042*
Post-2	10	1.61 ± 0.402	1.63	1.01–2.11
Pre	7	1.26 ± 0.209	1.28	1.01–1.54	0.028*
Post-3	7	1.54 ± 0.236	1.52	1.26–1.99
Post-1	10	1.61 ± 0.243	1.55	1.30–2.06	0.971
Post-2	10	1.61 ± 0.402	1.63	1.01–2.11
Post-1	7	1.56 ± 0.306	1.47	1.28–2.06	0.091
Post-3	7	1.54 ± 0.236	1.52	1.26–1.99
Post-2	7	1.67 ± 0.296	1.55	1.25–2.11	0.310
Post-3	7	1.54 ± 0.236	1.52	1.26–1.99
Notes: For numerical data, the P value was tested using the paired t-test when the data was normally distributed, with the Wilcoxon test as an alternative when the data was not normally distributed. Statistical significance is based on a P value < 0.05. CPR: Cerebroplacental Ratio

On the other hand, the P values for the CPR variable were greater than 0.05 (P > 0.05), indicating that the differences were not statistically significant. Thus, it can be concluded that there is no statistically significant difference in the mean CPR values between the Post-1 vs Post-2, Post-1 vs Post-3, and Post-2 vs Post-3 groups.

Figure 1

Figure 1. Correlation Analysis Between Vitamin D Levels Before and After Supplementation with CPR. Statistical significance is indicated by p < 0.05. *CPR: Cerebroplacental Ratio

A positive correlation was noted between Vitamin D levels and CPR (r = 0.358, P = 0.310), though it was not statistically significant.

Discussions

This study included 13 pregnant women with systemic lupus erythematosus (SLE) at 20–25 weeks of gestation. Two were excluded due to moderate–severe disease activity, and one due to pregnancy complications (vaginal bleeding and intrauterine fetal death). Pregnancy induces adaptive immune changes to tolerate paternal antigens expressed in fetal tissues, but this can also trigger autoimmune responses and SLE exacerbations. Hormonal shifts, particularly Th1 to Th2 dominance, can worsen Th2-mediated autoimmune responses in SLE [5, 6].

Exacerbation rates during pregnancy range from 13%–68%, often leading to irreversible organ damage and adverse pregnancy outcomes (APO). Musculoskeletal flares are less common, whereas renal and hematologic involvement is more frequent. Disease activity within 6–12 months before conception strongly predicts risk [6, 10]. Fetal APO include:

Fetal loss—spontaneous abortion (< 28 weeks, < 1000 g), therapeutic abortion, stillbirth (≥ 28 weeks), and neonatal death (< 28 days).

Preterm birth (< 37 weeks).

Small for gestational age (< 10th percentile).

Neonatal asphyxia (Apgar < 7 at 1 or 5 min).

Pregnancy flares are defined by new SLE symptoms, prednisone ≥ 0.5 mg/kg/day, addition of immunosuppressants, or SLEDAI increase ≥ 3. Mechanisms of APO include: activation of maternal/fetal hypothalamic-pituitary axis with increased corticotropin-releasing hormone, inflammatory cytokine surges (anti-dsDNA, hypocomplementemia), lower estradiol levels in SLE (linked with preterm labor), and use of prednisone [6–10]. Thus, immune dysregulation, autoantibodies, hormonal dysfunction, and treatment effects collectively drive complications [1, 6, 10].

Baseline characteristics: mean age 28.3 years (19–35). Literature shows SLE predominates in reproductive-aged women (6–10 times more frequent in females, ~ 90% in reproductive years) [1–4]. Jiang et al. reported ages 20–40 [4], Zhan and Gheita 27–29 years [30, 31]. Maternal age influences outcomes: >35 years increases preeclampsia, preterm birth, and fetal growth restriction, while younger age may increase flare risk due to heightened immune activity [6, 10, 32].

Vitamin D analysis: before supplementation (5000 IU/day × 3 months), mean level was 21.92 ± 4.852 ng/mL; after supplementation 35.85 ± 5.680 ng/mL (p = 0.005). Initially, 90% had hypovitaminosis; post-supplementation, 100% achieved normal levels (p = 0.004). A West Java study similarly showed 96% deficiency in first-trimester mothers [33]. Vitamin D status depends on sun exposure, diet, pigmentation, and lifestyle [34, 35]. In SLE, deficiency is exacerbated by long-term steroid/hydroxychloroquine use, renal involvement, and autoantibodies [36–41]. Supplementation reduces disease activity, improves complement levels, and lowers cytokines [42–47]. Nausheen et al. confirmed 4000 IU is safe in pregnancy [42]. Motamed et al. demonstrated 2000 IU reduced TNF-α and IL-6, improving neonatal outcomes [48]. Deficiency correlates with higher disease activity, anti-dsDNA titers, and lower complement [43–46]. Vitamin D may lower risk of preeclampsia, gestational diabetes, low birth weight, and preterm birth [44–49].

Cerebroplacental ratio (CPR), the middle cerebral artery pulsatility index (PI MCA) divided by umbilical artery PI (PI UA), is a Doppler marker of placental function. Cutoff: 1.08; values < 1.08 indicate risk of IUGR or stillbirth [50–52]. CPR reflects cerebral vasodilation from hypoxia and placental resistance. Studies confirm abnormal CPR (< 1) predicts APO, including growth restriction [9, 30, 31]. EULAR guidelines recommend intensive Doppler monitoring (umbilical, uterine, ductus venosus, MCA) in the third trimester [19, 30]. Jakubiec et al. found abnormal CPR more frequent with vitamin D deficiency; supplementation improved CPR values [20]. Low-dose supplementation (< 500 IU) was linked with worsening CPR, while 2000 IU improved indices.

At 20 weeks, CPR predicts later fetal size and APO better than MCA-PI or UA-PI alone [55]. Kumar et al. reported CPR cutoff 1.49 yielded sensitivity 67.5% and specificity 68% for IUGR detection [78]. In this study, vitamin D before supplementation had weak positive correlation with CPR (r = 0.228, p = 0.527), while after supplementation correlation was r = 0.358, p = 0.310—both nonsignificant. Nevertheless, evidence suggests vitamin D improves placental blood flow and CPR [20, 26]. Cohorts with supplementation reported higher CPR, better neonatal outcomes, and fewer NICU admissions [55, 56]. Animal and cell studies show vitamin D supports placental angiogenesis via VEGF upregulation and reduced anti-angiogenic factors (e.g., sFlt-1) [23, 24]. Low vitamin D increases spontaneous abortion risk [20, 23, 24]. Clinical reports indicate abnormal umbilical artery flow can be corrected by interventions enhancing placental vascularization, suggesting vitamin D plays a similar protective role.

Guidelines on vitamin D supplementation vary. WHO does not universally recommend supplementation, while EFSA and IOM advise 600 IU/day; RCOG suggests 400 IU/day; high-risk groups may need 1000 IU/day [15, 50]. Palacios et al. recommended maintaining ≥ 40 ng/mL, requiring up to 4000 IU/day depending on BMI, ethnicity, and sun exposure [13, 14]. RCTs show 2000–5000 IU/day is safe and effective, with IOM setting the upper limit at 4000 IU and the Endocrine Society at 10,000 IU [14]. Bokharee et al. demonstrated 5000 IU/day achieved target levels in 90–97% of pregnant women without adverse effects [56, 57].

Limitations

This study demonstrates that vitamin D supplementation in pregnancies complicated by SLE significantly increases serum vitamin D levels, potentially improves cerebroplacental ratio (CPR), and may contribute to better maternal–fetal outcomes. However, the small sample size limits the statistical power and generalizability of the findings. The quasi-experimental design without a control group also restricts causal inference. Despite these constraints, the results are consistent with existing evidence supporting the immunomodulatory and vascular benefits of vitamin D in pregnancy. Future large-scale randomized controlled trials are warranted to confirm these associations and further elucidate the mechanisms linking vitamin D status with fetal hemodynamic adaptation and pregnancy outcomes in SLE.

Conclusion

Vitamin D supplementation significantly increased serum levels and improved fetal CPR in pregnant women with SLE. These findings suggest potential benefits in optimizing fetal outcomes through Vitamin D supplementation. Larger-scale studies are necessary to confirm these findings.

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Declaration Ethics Approval and Informed Consent to Participate.

All methods were. carried out in accordance with relevant guidelines and regulations after obtaining approval and recommendations from the Ethics Committee Review Board of Hasan Sadikin General Hospital – Faculty of Medicine, Universitas Padjadjaran with reference number DP.04.03/D.XIV.6.5/148/2024. Since this study used secondary data, written informed consent was not applicable.

Consent for publication

Ethics Committee Review Board of Hasan Sadikin General Hospital – Faculty of Medicine, Universitas Padjadjaran waived the need for informed consent with reference number DP.04.03/D.XIV.6.5/148/2024.

Competing Interest

The authors have declared that no competing interest exist.

Funding

No funding

Acknowledgements

No applicable.

Data Availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Author Contribution

N.I: Conceptualization, methodology, writing—original draft, supervision.S.I: Conceptualization, methodology, validation, writing—review & editing.M.A.A: Conceptualization, methodology, writing—original draft.S.D: Investigation, validation, resources, writing—review & editing.A.D.N: Data curation, visualization, writing—review & editing.A.S: Data curation, formal analysis, project administration.A.D.A: Investigation, resources, validation, supervision.B.H: Investigation, resources, validation, supervision.J.S.E: Investigation, resources, validation, supervision.

All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work to ensure its integrity and accuracy.

Fig. 1

Correlation Analysis Between Vitamin D Levels Before and After Supplementation with CPR. Statistical significance is indicated by p < 0.05. *CPR: Cerebroplacental Ratio

Yes

Abstract

Objective: Pregnancy in women with systemic lupus erythematosus (SLE) carries increased maternal and fetal risks. Vitamin D plays an essential role in placental vascular function and fetal circulation regulation. The cerebroplacental ratio (CPR) reflects fetal adaptation to chronic hypoxia through the brain-sparing effect. This study aimed to evaluate the effect of vitamin D supplementation on fetal CPR in pregnant women with SLE. A quasi-experimental pretest–posttest study was conducted at Dr. Hasan Sadikin General Hospital, Bandung, from May to October 2024. Ten participants received 5000 IU of vitamin D daily for three months. Serum vitamin D and fetal CPR were measured monthly and analyzed using SPSS 24.0. Results Following supplementation, the mean serum vitamin D increased from 21.92 ± 4.85 ng/mL to 35.85 ± 5.68 ng/mL (p=0.05), with hypovitaminosis resolved in all subjects (p = 0.004). The mean CPR improved from 1.30±0.16 in month 1 to 1.61±0.24 in month 2 and remained stable in month 3 (p 0.0001). Thus, three months of 5000 IU vitamin D supplementation in pregnant women with systemic lupus erythematosus (SLE) leads to a noticeable change in vitamin D levels and fetal cerebroplacental ratio (CPR), but the effect on CPR shows a weak, non-significant correlation.