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Neonatal Respiratory Diseases - Unmasking Genetic Mechanisms

Neonatal Respiratory Diseases - Unmasking Genetic Mechanisms

Posted By HealthcareOnTime Team Posted on 2022-02-02

Today, Due to environmental conditions, pre-pregnancy pulmonary infections, lifestyle habits like Smoking, junk food, the ability to withstand the intra-uterine and extrauterine turbulence is critically altered in the past couple of decades. Accordingly, studies have revealed that almost 35% of neonates face breathing difficulties, and need assisted ventilation. even above 28 weeks of gestation. Surprisingly, the data excludes neonates who are born with congenital abnormalities and other common conditions seen in infants. Enough evidences gathered through several studies are also supporting the fact that there has been an exponential increase in several neonatal admission postpartum; due to increased respiratory complications in mothers as well as due to increased rate of c-section deliveries. Although, due to increased technological advancements and contemporary diagnostic facilities, the mortality rate has severely decreased over the period prompt administration of effective treatment regimens is highly crucial for better clinical outcomes.

Neonatal Respiratory Diseases - Unmasking Genetic Mechanisms

Accordingly, the present review specifies common respiratory conditions in neonates, risk factors, and clinical aspects (symptoms and causes) of all neonatal diseases. Here, we have summarized the genetic predisposition in neonates responsible for respiratory illness and respiratory dysfunctional attributes.

Common Neonatal Respiratory Challenges:
Respiratory Apnea
Respiratory apnea, also commonly known as respiratory distress syndrome is mainly reported in neonates with a congenital functional deficiency in the lungs. The deficiency is primarily associated with the lack of enough surfactant in the lungs, and can also be referred to as hyaline membrane disease. Some studies have also reported that infants born to pre-diabetic and/or diabetic mothers are at higher risk of suffering from respiratory apnea.

Although, production of surfactant is initiated on the 24th week of gestation by type 2 pneumocytes; the level can increase with increased gestational age, susceptibility to respiratory illnesses, and genetic predisposition associated with lung disease. The infant may start displaying the early signs of respiratory disturbances soon after birth and hence, will need immediate supportive ventilation. More in-depth analysis of acute respiratory distress syndrome involves chest radiograph with poorly inflated lungs along with ground grass appearance. The condition may advance in the first 24-48 hours of assisted ventilation stabilize after 24-48 hours followed by clinical improvement.

Transient Tachypnea It is one of the most reported conditions of neonatal respiratory distress syndrome; constituting more than 50% of the total neonatal issues. The condition is commonly associated with reversal of pulmonary residual fluid postpartum; which in ideal condition is removed with the help of dilated lymphatic vessels, to increase pulmonary circulation and retain breathing. Although, researchers are not able to pinpoint the genetic cause of the lung disease many commonly reported risk factors to include maternal asthma, maternal diabetic, c-section delivery, macrosomia to be possibly responsible for underlying condition. The clinical aspects include immediate respiratory distress within 1-2 hrs of birth; which can last up to 48 hrs. Fluid accumulation in the lung region can be confirmed through chest radiography. Many reported cases can be managed through conservative treatments along with supportive oxygen therapy.

However, in case of prolonged respiratory support or supplementary oxygen intake; an alternative diagnosis is generally referred to with diuretics.

Persistent Pulmonary Hypertension Persistent pulmonary hypertension is characterized by sudden failure of neonatal respiratory vasculature to adapt to the changing environment from intra-utero to ex-utero, following birth. Studies have indicated that the sudden collapse is a secondary clinical sign of an associated lung disorder. The reported prevalence of the condition so far is around 1 in 1000 births and is found to be mainly connected with congenital birth abnormalities, congenital diaphragmatic hernia, maladaptation, etc. Many of these maladaptations, i.e. reported failure of infants to adapt to the external environment are observed to be the complications of perinatal asphyxia, other known/unknown lung infections, and/or lung parenchyma diseases. Other studies have also linked genetic predisposition along with chromosomal abnormalities to be responsible for lung disorders.' Researchers have also pinpointed the fact that maternal medications at the time of pregnancy can also challenge the smooth lung functioning of the baby.

Early diagnosis of persistent pulmonary hypertension is observed to be quite difficult as the signs and symptoms are found to be quite in line with other congenital disorders. However, certain clinical assessments like the right to left shunting assessments are based on the pre and post ductal oxygen saturation levels.

Persistant pulmonary hypertension studies have pinpointed the fact that it can directly or indirectly impact neonatal survival rate with significant neurodevelopmental disabilities by the age of 2.

Meconium Aspiration Syndrome The full-term healthy fetus tends to pass meconium into the amniotic fluid, before the delivery; if it experiences significant stress or discomfort during delivery. Some studies have connected the phenomena of passing meconium with fetal distress, while the fetus is trying to cope up with respiratory attempts. Previous reports have suggested that during such gasping process, there is a chance of fetal discomfort due to meconium inhalation into the lungs which can further give rise to many adverse conditions like chemical pneumonitis, lung infections, obstruction of pulmonary airways, surfactant disturbance, etc.

Statistical analysis done on the same has demonstrated that almost 0.43 per 1000 live births can report meconium aspiration syndrome; requiring immediate assisted respiratory support. Studies have also proposed that male sex of the fetus, increased maternal age, reduced APGAR score are some of the common risk factors assessed for the condition.

For effective clinical assessments routine hospital observation is advised especially in infants who have passed the meconium in-utero. Some neonates may display signs of respiratory distress including ischemic encephalopathy due to hypoxia, convulsions, vomiting, etc. Further, chest radiograph can display patchy lungs and lung inflammation.

Management of infants exhibiting signs of meconiuminduced lung distress revolves around supportive therapeutic modules, including oscillatory ventilation, Extra Corporeal Membrane Oxygenation (ECMO), antibiotic therapy, exogenous surfactant therapy, etc. The preliminary aim of these therapies is to reduce lung inflammation as well as decrease associated lung infection.

Congenital Pneumonia The condition is described as an early onset, mostly associated with trans-placental infections, higher maternal age, rubella infections, etc. Studies have reported Group B Streptococcus as one of the primary factors responsible for the conditions. Some other investigations have proposed that improperly done amniocentesis can be responsible for initiating infections in the amniotic fluid; which further if inhaled by a full-term fetus can result in pneumonia or other respiratory infections. Accordingly, as per current guidelines proposed by regulatory authorities, amniocentesis should be accompanied by the administration of intrapartum antibiotics.

Apart from the above mentioned, multiple other risk factors have been stated including pre-labor rupture of amniotic membrane for a prolonged period, preterm birth, intrapartum fever higher than 38??C, along with chronic bacterial infections to mother.

It should also be noted that there are cases of late-onset of pneumonia as well, reported immediately after the birth. Infants who have been on mechanical ventilation are more vulnerable to pneumonia or other respiratory infections and are mostly considered to be hospitalacquired.

The clinical assessments are mostly dependent upon the signs of respiratory distress in neonates, along with a chest radiograph showing multiple patches in the lungs with inflammation. The immediate administration of antibiotics is referred to as the mainstay treatment in the current condition; however, other supportive treatments like oxygen therapy, etc., are also advised depending upon the requirement to avoid dangerous consequences.

Experts believe that period immediately after birth is quite critical for the future well-being of a baby as well as a mother, may it be pre-term delivery or full term. The infant has to go through many physiological changes during the process, and hence is quite vulnerable to range of respiratory challenges in his extra-uterine life. Through proper clinical assessments, thorough investigations, genetic testing for neonatal respiratory diseases, and other appropriate investigations; these signs and conditions of respiratory illnesses can surely be prevented. Further, accurate diagnosis is the key to correct treatment applications, and hence, one should make sure that the clinicians who are taking care of the infants have vast experience and wide knowledge about these clinical manifestations, and further reducing the mortality rate.

 

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