Maternal Lifestyle and Neonatal Hypoglycemia

Repercussion of Maternal Lifestyle on Obstetric and Neonatal Outcomes

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Sedentary Lifestyle; Pregnancy; Hyperinsulinemia; Miscarriages
• Intervention / Treatment: Behavioral: Daily brisk walking plus a carbohydrate-restricted diet

Detailed Description

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
• Enrollment (Actual): 480
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20221-903
      • Hospital Federal dos Servidores do Estado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lifestyle counseling; Daily brisk walking plus a carbohydrate-restricted diet	Behavioral: Daily brisk walking plus a carbohydrate-restricted diet; 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.
No Intervention: Standard follow-up; Prenatal care will proceed according to the routine.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy and Neonatal Outcomes	Early miscarriages, 2nd and 3rd trimester losses, preterm deliveries, take-home babies, neonatal hypoglycemia: number of babies	Three years

Collaborators and Investigators

• Sponsor: Hospital dos Servidores do Estado do Rio de Janeiro
• Collaborators: Rio de Janeiro State Research Supporting Foundation (FAPERJ)
• Investigators: Principal Investigator: Maria A Sayeg-Porto, MD, PhD, Hospital dos Servidores do Estado, RJ; Universidade Federal do Rio de Janeiro; Principal Investigator: Paulo R Benchimol-Barbosa, MD, DSc, Universidade Gama Filho; COPPE/UFRJ; Principal Investigator: Silvia Hoirisch-Clapauch, MD, Hospital dos Servidores do Estado, RJ

Publications and helpful links

General Publications

• Hoirisch-Clapauch S, Porto MAS. Early neonatal hypoglycemia prediction according to maternal parameters. Thrombosis Research 131(1): S96, 2013.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: August 3, 2011
• First Posted (Estimate): August 4, 2011

Study Record Updates

• Last Update Posted (Estimate): September 29, 2016
• Last Update Submitted That Met QC Criteria: August 19, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: physical activity; pregnancy; preterm delivery; sedentary lifestyle; neonatal hypoglycemia; high-glycemic index diet; take-home baby; recurrent miscarriages
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Pregnancy Complications; Hypoglycemia; Hyperinsulinism; Abortion, Spontaneous
• Other Study ID Numbers: 000416-09-08-2010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes