Preeclampsia reduced by Vitamin D - many studies

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Preeclampsia risk reduced by supplements (Calcium, Vitamin D, etc) - Feb 2025

Dietary supplements and prevention of preeclampsia
Review Hypertens Res. 2025 Feb 10. doi: 10.1038/s41440-025-02144-9
Takafumi Ushida 1 2, Sho Tano 3 4, Seiko Matsuo 3 4, Kazuya Fuma 3 4, Kenji Imai 3 4, Hiroaki Kajiyama 3, Tomomi Kotani 3 4

Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE.
In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE.
Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan.
According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions.
We also reviewed other dietary supplements, including

• vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins),
• minerals (magnesium, zinc, and iron),
• amino acids (l-arginine and l-carnitine),
• anti-oxidants (lycopene, resveratrol, and astaxanthin), and
• other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol).

In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE.
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Fewer than 1% of pregnancies result in major Preeclampsia problems (HELLP)

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The day she had a baby, she lost her memory Washington Post Feb 2025
refers to book: Pieces You'll Never Get Back: A Memoir of Unlikely Survival

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Preeclampsia increases the risk of epilepsy by 5.3X - Jan 2025

MD Edge
See also: Overview Epileptic children and Vitamin D

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Preeclampsia rate reduced 3X by Vitamin D (60,000 IU once a month) - RCT Feb 2024

Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women: a randomised clinical trial in Eastern Democratic Republic of the Congo
BMC Pregnancy Childbirth. 2024 Feb 3;24(1):107. doi: 10.1186/s12884-024-06277-6.
Richard Kabuseba Kabuyanga 1, Pierrot Lundimu Tugirimana 2, Balungwe Sifa 3, Mwanga Balezi 4, Michel Ekanga Dikete 5, Prudence Ndeba Mitangala 6, Jean Pierre Moyene Elongi 7, Xavier Kalume Kinenkinda 8, Jean-Baptiste Sakatolo Zambeze Kakoma 9

Vitamin D levels in ng?   Non-supplemented had higher levels of vitamin D?

Background: Previous studies have reported the association between maternal vitamin D deficiency and preeclampsia. However, the efficacy of vitamin D supplementation in reducing the occurrence of preeclampsia remains unclear. The objective of this study was to evaluate the effect of cholecalciferol supplementation on the incidence of preeclampsia in primigravid women and its related maternal and foetal outcomes.

Methods: A single-blinded clinical trial was conducted in fourteen antenatal care health facilities in the North (Goma, Mwesso, Nyiragongo) and South Kivu (Bukavu-Panzi) provinces of the Democratic Republic of Congo from March 1, 2020, to June 30, 2021. A total of 1300 primigravid women not exceeding 16 weeks of gestation were randomised with a 1:1 ratio to either the supplemented (A) or control (B) group. Each pregnant woman (A) presenting for antenatal care received a single monthly dose of cholecalciferol (60,000 IU) orally for 6 months. The control group received no vitamin D supplementation or placebo. Serum 25(OH)D was measured at recruitment and at 34 weeks of gestation. Outcomes were assessed monthly until delivery.

Results: The median maternal age was 21 years (14-40), while the median gestational age was 15 weeks (5.4-29.0).

• A significant reduction in the risk of preeclampsia [RR = 0.36 (0.19-0.69); p = 0.001] and
• preterm delivery [RR = 0.5 (0.32-0.78); p = 0.002] was observed in the intervention group.
• An RR of 0.43 [(0.27-0.67); p < 0.001] was found for low birth weight.
• The RR for caesarean section was 0.63 [(0.52-0.75); p < 0.001].
• The APGAR score at the 5th minute (p = 0.021) and the
• size of the newborn were significantly higher in the supplemented group (p = 0.005).

Conclusion: A single monthly dose (60,000 IU) of vitamin D supplementation, started in early pregnancy, significantly reduced the incidence of preeclampsia and its maternal and foetal complications.
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Preeclampsia = hypertension (high blood pressure) during pregnancy

  click here for details

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Preeclampsia 4.3 X more likely if low vitamin D - meta-analysis Nov 2023

Vitamin D and preeclampsia: A systematic review and meta-analysis
SAGE Open Med . 2023 Nov 22:11:20503121231212093. doi: 10.1177/20503121231212093
Abdulla AlSubai 1, Muhammad Hadi Baqai 2, Hifza Agha 3, Neha Shankarlal 4, Syed Sarmad Javaid 5, Eshika Kumari Jesrani 2, Shalni Golani 6, Abdullah Akram 4, Faiza Qureshi 6, Shaheer Ahmed 4, Simran Saran 7

Preeclampsia RCTs: 4.3 X high risk if low Vitamin D

Objectives: Preeclampsia is one of the most frequent pregnancy disorders, with a global incidence of 2%-8%. Serum 25-hydroxyvitamin D is an essential mineral for human health; some studies suggest link between 25-hydroxyvitamin D deficiency and preeclampsia, while others offer contradictory findings. Thus, the goal of this study is to evaluate the relationships between maternal 25- hydroxyvitamin D concentrations and the risk of preeclampsia. In addition to this, our study also evaluates the effects of 25- hydroxyvitamin D supplementation on the incidence of preeclampsia. Therefore, assessing 25- hydroxyvitamin D's potential as a possible intervention to lower the risk of preeclampsia.

Methods: The Medline database was queried from inception until July 2021 for randomized controlled trials and observational studies without any restrictions. The studies assessing the association between 25-hydroxyvitamin D deficiency and preeclampsia and the impact of 25-hydroxyvitamin D supplementation on the incidence of preeclampsia were incorporated. The results were reported using a random-effects meta-analysis and the Mantel-Haenszel odds ratio. A p-value of <0.05 was considered significant for the analysis.

Results: This analysis includes 34 papers, including 10 randomized controlled trials and 24 observational studies. According to our pooled analysis, 25-hydroxyvitamin D supplementation was significantly associated with a lower risk of preeclampsia in pregnant women (OR: 0.50; 95% CI: 0.40-0.63; p = 0.00001), while 25-hydroxyvitamin D deficiency was significantly associated with an increased risk of preeclampsia (OR: 4.30; 95 % CI: 2.57-7.18; p < 0.00001, OR: 1.71; 95 % Cl: 1.27-2.32; p = 0.0005, OR 1.61; 95 % Cl: 1.21-2.16; p = 0.001).

Conclusion: Results suggest that 25-hydroxyvitamin D has a significant relationship with preeclampsia as confirmed by the findings that low maternal 25-hydroxyvitamin D concentrations cause increased risk of preeclampsia while 25-hydroxyvitamin D supplementation reduces the incidence of preeclampsia. Our findings indicate that 25-hydroxyvitamin D supplementation can be used as a possible intervention strategy in preventing one of the most common causes of maternal mortality around the world, preeclampsia.
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Preeclampsia 3X more likely if low vitamin D in mid-pregnancy - May 2023

Association of maternal vitamin D status with the risk of preeclampsia
Food Funct. 2023 May 22;14(10):4859-4865. doi: 10.1039/d3fo00007a   PDF is behind a paywall
Juhi Nema 1, Nisha Wadhwani 1, Karuna Randhir 1, Kamini Dangat 1, Hemlata Pisal 1, Vrushali Kadam 1, Savita Mehendale 2, Girija Wagh 2, Bharati Kulkarni 3, Harshpal Singh Sachdev 4, Caroline Fall 5, Sanjay Gupte 6, Sadhana Joshi 1

The aim of this study was to examine serum vitamin D concentrations from early pregnancy until delivery in women who did and did not develop preeclampsia. This longitudinal study was carried out in Pune, India. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from two hospitals. Blood samples were collected and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks and V4 = at delivery. 108 women who developed preeclampsia (PE) and 216 who did not develop PE (Non-PE) were randomly selected from the remainder. Serum 25-hydroxy vitamin D concentrations (25(OH)D) were estimated in their samples using commercially available ELISA kits. Independent t-tests were used to compare 25(OH)D between PE and non-PE groups. Logistic and linear regressions were used to examine associations of 25(OH)D with the risk of preeclampsia and birth outcomes, respectively, after adjusting for confounders. The mean (SD) 25(OH)D at V1 was 21.95 (19.64) in the Non-PE group and 17.76 (13.21) in the PE group.
A decrease in the concentrations of vitamin D (ng ml-1) in mid-pregnancy (V2) and at delivery was associated with an increased risk of preeclampsia (0.31 [95% CI 0.11, 0.86], p = 0.024 and 0.24 [95% CI 0.08, 0.77], p = 0.016), respectively. Our finding of lower vitamin D concentrations in mid-pregnancy, before women developed clinical preeclampsia, suggests that vitamin D may have a role in its pathophysiology.

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Preeclampsia 4 X more-likely if poor Vitamin D Receptor - Aug 2023

Impact of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism on the risk of developing preeclampsia
Biochemistry and Biophysics Reports Vol 35, Sept 2023, 101526 https://doi.org/10.1016/j.bbrep.2023.101526
Md Mostafijur Rahman a 1, Tamima Nawfal a 1, Fabliha Afiea Khabir a 1, Md Bayejid Hosen a, Mubasshir Washif a, Yearul Kabir b, M Zakir Hossain Howlader a

Objective
Preeclampsia is a multifactorial disease characterized by high blood pressure and protein in the urine. In this study, we investigated the association of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism with the risk of developing preeclampsia.

Methods
25-hydroxyvitamin D was measured using High-performance Liquid Chromatography. Vitamin D binding protein and vitamin D receptor gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism.

Results
The control subjects have significant higher level of 25-hydroxyvitamin D (33.5 ± 1.194 ng/mL) relative to patients (23.97 ± 1.604 ng/mL) (p < 0.05). Vitamin D receptor rs1544410 and rs2228570 dominant model (GA + AA; TC + CC) showed significant higher risk of developing Preeclampsia (OR = 4.11, 95% CI = 0.62–27.09, p < 0.01; OR = 3.58, 95%CI = 0.78–16.38, p < 0.001 respectively). Similarly, vitamin D binding protein rs7041 and rs4588, dominant model (TG + GG; CA + AA) showed higher risk of preeclampsia development compared to control people (OR = 1.69, 95%CI = 0.35–8.19, p < 0.05; OR = 1.06, 95%CI = 0.25–4.44, p < 0.05 respectively). AA genotype of rs4588 of GC gene was significantly associated with 25-hydroxyvitamin D level in serum relative to CC and CA (p < 0.05).

Conclusion
From our study, we can conclude that a low level of 25-hydroxyvitamin D, GC (rs1544410 and rs2228570), and VDR (rs4588 and rs7041) gene polymorphism is linked with an increased risk of developing preeclampsia.
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Preeclampsia 1.5 more-likely if poor Vitamin D Receptor - meta-analysis April 2023

Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis
PeerJ. 2023 Apr 25;11:e15181. doi: 10.7717/peerj.15181
Yicong Guo # 1, Yu Zhang # 2, Xiangling Tang 2, Xionghao Liu 2, Huilan Xu 1

Background: Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility.

Methods: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity.

Results: A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07-1.79]; P = 0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12-1.95]; P = 0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21-3.52]; P = 0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians.

Conclusion: The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.
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Could Vitamin D Be Effective in Prevention of Preeclampsia? - Oct 2021

Nutrients 2021, 13(11), 3854; https://doi.org/10.3390/nu13113854
by Elżbieta Poniedziałek-Czajkowska and Radzisław Mierzyńsk
Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-954 Lublin, Poland

(This article belongs to the Special Issue Role of Vitamin D Deficiency in Pregnancy Disorders)

Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.

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Preeclampsia Vitamin DTrials

more columns are in the PDF

Preeclampsia meta-analyses

Conclusions

Currently, the commonly recommended preeclampsia prophylaxis is the use of low doses of acetylsalicylic acid in high-risk pregnant women and, by some institutions, calcium supplementation in groups with its deficiencies in the diet. Numerous studies are being conducted on the use of other substances and drugs for this purpose, which, due to their properties and mechanisms of action, could prevent the development of preeclampsia. One of these thoroughly studied substances is vitamin D. Based on the results of research explaining its mechanism of action and understanding the reasons and pathophysiology of the development of preeclampsia, it might be postulated that an anti-inflammatory effect of Vit D and its beneficial influence on the endothelium constitutes its potential use in PE prevention. Unfortunately, the results of the randomized controlled trials and meta-analyses are ambiguous. Despite the multitude of studies published on this subject, there are no clear conclusions about its effectiveness in PE prevention which could form the basis for developing universal recommendations.
In the light of the available data, the following issues regarding the role of vitamin D in preventing preedampsia remain unresolved:

• 1. Should the target group for vitamin D supplementation be all pregnant women or only those at high risk?
• 2. Should it be recommended to test the vitamin D concentration in the periconceptional period and the early first trimester in all pregnant women or a high-risk group?
• 3. Since when (during the planning period of pregnancy or in the first trimester),
  • how long and what doses of vitamin D should be proposed considering the safety of offspring?
• 4. What vitamin D level in the periconceptional period and the first trimester should be considered sufficient?

These questions may determine the direction of research on vitamin D in the prevention of preeclampsia.
It seems that the fundamental issue, despite the extensive literature, remains the assessment of Vit D concentration in the periconceptional period and/or the early first trimester and defining levels that would allow reducing the risk of PE development. Women with risk factors for Vit D deficiency such as obesity, kidney, liver, thyroid gland diseases, chronic bowel diseases, autoimmune diseases, asthma, diabetes t.2, hypertension, and chronic glucocorticoids, antiepileptic and antiretroviral drug treatment would benefit the most from screening. It appears that patients with risk factors for PE development and Vit D deficiency may require higher doses of vitamin D than commonly recommended for pregnant women.
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55+ VitaminDWiki pages with PREECLAMPSIA in title

This list is automatically updated

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Preeclampsia before 34th week increased risk of early-onset dementia by 4 X - June 2024

BP Disorder in Pregnancy Tied to Young-Onset Dementia Risk MD Edge

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USPSTF wants to screen all pregnacies for hypertension - Feb 2023

USPSTF backs screening for hypertensive disorders of pregnancy MDEdge
U.S. Preventive Services Task Force = USPSTF
16% of US pregnancies had hypertension in 2019

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VutaminDWiki - Hypertension category contains

169 items in the category HYPERTENSION

see also
Overview Overview Hypertension and Vitamin D
Overview Cardiovascular and vitamin D
Overview Stroke and vitamin D
Incidence of 22 health problems related to vitamin D have doubled in a decade
Some interesting Hypertension studies

• Hypertension risk decreased 10X by increasing vitamin D levels to more than 40 ng – Nov 2017
• Hypertension risk reduced 4X if adequate level of Vitamin D – July 2024
• COVID-19 deaths 4 to 7 X more likely if Diabetic, Hypertensive, or CVD - meta-analysis March 2020
• Magnesium reduces hypertension - FDA allows claim - Jan 2022
• Drug-resistant hypertension 3.5 X more likely if low vitamin D – March 2020
• High Blood Pressure reduced by Vitamin D supplementation in seniors and obese – meta-analysis May 2019
• Blood pressure in diabetics reduced by 12 weekly doses of 50,000 IU vitamin D – RCT Jan 2014
• Hypertension is associated with low vitamin D in some groups – meta-analysis April 2015
• Off Topic – Hypertension in 42 percent of adults (new definition: 130 mm Hg) – Feb 2018
  • Men aged 40-59 59%, age >60 75%: National Health and Nutrition Examination Survey, 2017–2018

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VitaminDWiki - Pregnancy category contains

942 items in Pregnancy category

 - see also

• Overview Pregnancy and vitamin D
• Number of articles in both categories of Pregnancy and:Dark Skin 30;   Depression 21;   Diabetes 45;   Obesity 18;  Hypertension 44;   Breathing 37;  Omega-3 46;  Vitamin D Receptor 25 Click here for details
• All items in category Infant/Child 867 items
• Pregnancy needs at least 40 ng of vitamin D, achieved by at least 4,000 IU – Hollis Aug 2017
• 38+ papers with Breastfed etc, in the title
• Call to action – more Vitamin D for pregnancies, loading doses are OK – Holick Aug 2019
• 53+ preeclampsia studies
• 94+ studies with PRETERM in the title
• Fertility problem (PCOS) reduced by vitamin D, etc: many studies 15+
• 94+ Gestational Diabetes
• Caesarean birth much more likely if low Vitamin D - many studies 15+ studies
• Post-partum depression and low Vitamin D - many studies 15+ studies
• Stillbirth reduced by Vitamin D, Zinc, Omega-3 - several studies 5+ studies
• Search VitaminDWiki for "Assisted reproduction" 33 items as of Aug 2022
• Fertility and Sperm category listing has 146 items along with related searches
• (Stunting OR “low birth weight” OR LBW) 1180 items as of June 2020
• Less labor pain if higher level of vitamin D – August 2021
• Healthy pregnancies need lots of vitamin D
• Ensure a healthy pregnancy and baby - take Vitamin D before conception
  

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VitaminDWiki - Healthy pregnancies need lots of vitamin D contains

Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
   Click on hyperlinks for details

Problem	Vit. D Reduces	Evidence
0. Chance of not conceiving	3.4 times	Observe
1. Miscarriage	2.5 times	Observe
2. Pre-eclampsia	3.6 times	RCT
3. Gestational Diabetes	3 times	RCT
4. Good 2nd trimester sleep quality	3.5 times	Observe
5. Premature birth	2 times	RCT
6. C-section - unplanned	1.6 times	Observe
Stillbirth - OMEGA-3	4 times	RCT - Omega-3
7. Depression AFTER pregnancy	1.4 times	RCT
8. Small for Gestational Age	1.6 times	meta-analysis
9. Infant height, weight, head size      within normal limits		RCT
10. Childhood Wheezing	1.3 times	RCT
11. Additional child is Autistic	4 times	Intervention
12.Young adult Multiple Sclerosis	1.9 times	Observe
13. Preeclampsia in young adult	3.5 times	RCT
14. Good motor skills @ age 3	1.4 times	Observe
15. Childhood Mite allergy	5 times	RCT
16. Childhood Respiratory Tract visits	2.5 times	RCT

RCT = Randomized Controlled Trial

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Preeclampsia risk reduced 15% by taking baby aspirin daily - NYT May 2024

vs 70% reduction with Vitamin D taken once a month - see RCT on this page
 PDF

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