Maternal Lifestyle and Neonatal Hypoglycemia

Study Overview
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Brief Summary
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tPA has a pivotal role in placentation, mediationg activation of growth factors, such as vascular endothelial growth factor and brain-derived neurotrophic factor, degradation of extracellular matrix and basement membrane (directly or through activation of matrix metalloproteinases) and formation of hemidesmosomes. A high-carbohydrate intake combined with lack of physical activity provides a strong stimulus for maternal insulin production. In this scenario, either β-cells are dysfunctional and diabetes supervenes, or excessive amounts of insulin are produced, providing pathological stimulation of PAI-1 synthesis. Given that PAI-1 is a major tPA inhibitor, PAI-1 excess may affect placentation, increasing the risk of first trimester losses, preterm deliveries and intrauterine growth restriction. Our hypothesis was that prematurity was not the cause of neonatal hypoglycemia, but a parallel occurrence of a strong stimulus for maternal, fetal and neonatal production of insulin.

Detailed Description
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In an observational study, we sought to determine whether markers of hyperinsulinemia or situations that increase maternal insulin requirements would increase the risk of neonatal hypoglycemia. Mothers were selected if they had grade III obesity, acanthosis nigricans (surrogates of chronic maternal hyperinsulinemia), any invasive bacterial infection or if they had used corticosteroid within seven days before delivery (surrogates of subacute insulin resistance), if they reported to have consumed a high-glycemic index diet within 24 hours before delivery or if they were physically inactive within 24 hours before delivery (conditions that could increase maternal insulin requirements close to delivery). Based on the finding that that the risk of neonatal hypoglycemia increased fivefold with inactivity (95% CI: 2-11, P <0.001), 11-fold with high-carbohydrate intake (95% CI: 4-24, P <0.001) and 329-fold with both risk factors (95% CI: 32-3362, P <0.001), next we have evaluated how a protocol combining exercises and a balanced diet throughout pregnancy influences maternal and neonatal outcomes. One of the outcomes analyzed was neonatal hypoglycemia.

Official Title
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Repercussion of Maternal Lifestyle on Obstetric and Neonatal Outcomes

Conditions
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Hyperinsulinemia, Miscarriages, Pregnancy, Sedentary Lifestyle, Hypoglycemia

Intervention / Treatment
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* Behavioral: Daily brisk walking plus a carbohydrate-restricted diet


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: recurrent early unexplained miscarriages Exclusion criteria: (i) antiphospholipid antibodies, (ii) second- or third-trimester losses, (iii) multiple pregnancy, (iv) anatomical abnormalities that could increase the risk of early miscarriages, (iv) any condition requiring a priori anticoagulation, (v) protocol violation.

Ages Eligible for Study
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Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lifestyle counseling<br>Daily brisk walking plus a carbohydrate-restricted diet | Behavioral: Daily brisk walking plus a carbohydrate-restricted diet<br>* Daily brisk walking at moderate speed (4 km/h) for at least 40 minutes per day, 7 days a week. Patients will be recommended to avoid high-glycemic index meals (such as snacks, candies, fiber-free juices and sugar-sweetened beverages), and to eat at least two daily servings of meat, poultry, fish (e.g. 2 g/kg) or other protein-rich food, starting when they decided to get pregnant and continuing until delivery. Recommendations will be emphasised at every appointment. Antidepressants will not be discontinued in both groups, but patients on paroxetine and sertraline, will be switched to fluoxetine.<br>|
| No Intervention: Standard follow-up<br>Prenatal care will proceed according to the routine. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal Hypoglycemia | Any glucose level equal or below 40mg/dL at 1, 2 or 4 h after birth, obtained by heelstick. | 1, 2 and 4 h after birth. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Refractory Hypoglycemia | Any glucose level ≤ 40/dL at 1, 2 or 4 h: Neonates with hypoglycemia (glucose level equal or below 40 mg/dL at 1, 2 or 4 h) will be offered milk. Neonates unable to suckle, will be treated with intravenous dextrose for one hour. A new heel stick blood sample will be drawn to assess glucose levels. Neonates with persistent hypoglycemia will be considered as refractory hypoglycemia. | One hour after feeding or after intravenous dextrose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonatal hypoglycemia, pregnancy, physical activity, sedentary lifestyle, high-glycemic index diet, take-home baby, recurrent miscarriages, preterm delivery