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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
480
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.
Hospital Federal dos Servidores do Estado
Rio de Janeiro, Rio de Janeiro, Brazil
Neonatal Hypoglycemia
Any glucose level equal or below 40mg/dL at 1, 2 or 4 h after birth, obtained by heelstick.
Time frame: 1, 2 and 4 h after birth.
Refractory Hypoglycemia
Any glucose level ≤ 40/dL at 1, 2 or 4 h: 1. 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. 2. A new heel stick blood sample will be drawn to assess glucose levels. 3. Neonates with persistent hypoglycemia will be considered as refractory hypoglycemia.
Time frame: One hour after feeding or after intravenous dextrose
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