The Effect of Lifestyle Intervention for Hypertriglyceridemia on the Pathogenesis of Adverse Pregnancy Outcome

Study Overview
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Brief Summary
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During pregnancy, hypertriglyceridemia is associated with adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes mellitus, large for gestational age (LGA), and preterm delivery. However, whether lifestyle intervention for hypertriglyceridemia during pregnancy improves pregnancy outcomes remains unknown. Therefore, we will conduct a randomized controlled trial to investigate this issue. At a tertiary medical center, we will enroll 70 pregnant women in this prospective, open-label, randomized controlled, pilot study comparing the effect of lifestyle intervention for hypertriglyceridemia versus control between Mar 2020 and Mar 2022. Pregnant women recruited will be randomized into two groups. The intervention group will receive lifestyle intervention; whereas the control group will receive regular surveillance only. Only intervention group will have diet education and exercise goal. They will go to dietitian OPD twice at GA 30-31+6 and 33-34+6 for Mediterranean diet education. As for exercise, participants in intervention group are asked to at least take 10000 steps 3 days a week. Diet modification and exercise intervention will persistent until delivery. The primary end point is the change of biomarkers of preeclampsia and macrosomia, including maternal blood PlGF and sFLT1, and cord blood c-peptide, leptin, IGF-1, IGF-2, IGF-BP1 and IGF-BP3. The secondary end points include the change of frequency of adverse pregnancy outcomes, including individual outcome and the composite outcome, such as gestational hypertension, preeclampsia, preterm delivery, and large for gestational age (defined as birth weight ≥ 90th percentile), change of maternal body weight, change of maternal blood pressure, which is defined as 3 mm-Hg, change of maternal HOMA2-IR, change of maternal plasma triglyceride level and other lipid profile (total cholesterol, HDL, and LDL), echography finding of fetus, neonatal birth weight, change of glucose, and lipid profile (total cholesterol, HDL, LDL, and TG) of fetus cord blood, placental expression of preeclampsia (PlGF, sFLT1) and growth factors (IGF-1, 2, BP1 and BP3).

Official Title
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The Effect of Lifestyle Intervention for Hypertriglyceridemia on the Pathogenesis of Adverse Pregnancy Outcome: the LITAPO Randomized Trial

Conditions
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Hypertriglyceridemia During Pregnancy

Intervention / Treatment
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* Behavioral: Lifestyle including optimal exercise and diet modification.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women older than 20-year-old During GA 24-28+6 weeks Carrying a singleton Having hypertriglyceridemia (plasma triglyceride at GA 24-28+6 excess 246 mg/dL but not higher than 1000 mg/dL). Exclusion Criteria: Using steroid Using anti-platelet or anti-coagulant Using lipid-lowering agents Hypertriglyceridemia is caused by secondary cause, such as hypothyroidism, cushing syndrome, nephrotic syndrome, alcohol use or medication use. Have been diagnosed with chronic hypertension, overt diabetes mellitus, gestational diabetes mellitus, secondary hypertriglyceridemia, autoimmune disease, or malignancy. Have received the artificial fertilization. Not having fetus echography examination at GA 22-23+6 Not going to deliver the baby at National Taiwan University Hospital Have underwent other clinical trials

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention group receives lifestyle intervention for hypertriglyceridemia. | Behavioral: Lifestyle including optimal exercise and diet modification.<br>* The intervention group will receive diet education and be given exercise suggestion.<br>|
| No Intervention: Control<br>Control group receives regular surveillance. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of biomarkers of preeclampsia | including maternal blood PlGF (pg/mL) and sFLT1 (pg/mL) | Through study completion, an average of 2 year | 
| Change of biomarkers of macrosomia | such as cord blood c-peptide (μg/L) | Through study completion, an average of 2 year | 
| Change of biomarkers of macrosomia | such as cord blood leptin (ng/mL) | Through study completion, an average of 2 year | 
| Change of biomarkers of macrosomia | such as cord blood IGF-1 (ng/mL), IGF-2 (ng/mL) | Through study completion, an average of 2 year | 
| Change of biomarkers of macrosomia | such as cord blood IGF-BP1 (μg/mL), and IGF-BP3 (μg/mL) | Through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of frequency of adverse pregnancy outcomes, including individual outcome and the composite outcome | such as gestational hypertension, preeclampsia, preterm delivery, and large for gestational age | Through study completion, an average of 2 year | 
| Change of maternal body weight | Maternal body weight change (kilograms) | Through study completion, an average of 2 year | 
| Change of maternal plasma triglyceride level (mg/dL) and other lipid profile (total cholesterol, HDL, and LDL) | Other lipid profile including total cholesterol (mg/dL), HDL (mg/dL), and LDL (mg/dL) | Through study completion, an average of 2 year | 
| Change of maternal blood pressure | which is defined as 3 mm-Hg | Through study completion, an average of 2 year | 
| Change of maternal homeostatic model assessment 2 insulin resistance indexes (HOMA2-IR) | Maternal HOMA2-IR change. The higher level of HOMA2-IR means the higher risk for insulin resistance. | Through study completion, an average of 2 year | 
| Change of glucose level of fetus cord blood | Change of glucose level (mg/dL) of fetus cord blood | Through study completion, an average of 2 year | 
| Change of lipid profile of fetus cord blood | including TG (mg/dL), total cholesterol (mg/dL), HDL (mg/dL), and LDL (mg/dL) | Through study completion, an average of 2 year | 
| Echography finding of fetus | including biparietal diameter (mm), femur length (mm), head circumference (mm), and abdominal circumference (mm) | Through study completion, an average of 2 year | 
| Echography finding of fetus | including estimated fetal weight (gm) | Through study completion, an average of 2 year | 
| Neonatal birth weight | Neonatal birth weight (grams) | Through study completion, an average of 2 year | 
| Placental protein expression (immunohistochemistry or western blot) of preeclampsia biomarkers | including PlGF and sFLT1 | Through study completion, an average of 2 year | 
| Placental protein expression (immunohistochemistry or western blot) of growth factors | including IGF-1, IGF-2, IGF-BP1, and IGF-BP3 | Through study completion, an average of 2 year |