Association of asymptomatic structural cardiac defects in neonates with transient tachypnea at birth: A case-control study

Gurpreet Kaur Dhillon; Shankar Narayan; Ananthakrishnan Ramamoorthy; Harpreet Singh Dhillon; Shibu Sasidharan

doi:10.4103/jpai.jpai_5_21

ORIGINAL RESEARCH

Year : 2020 | Volume : 9 | Issue : 4 | Page : 140-145

Association of asymptomatic structural cardiac defects in neonates with transient tachypnea at birth: A case-control study

Gurpreet Kaur Dhillon¹, Shankar Narayan², Ananthakrishnan Ramamoorthy³, Harpreet Singh Dhillon⁴, Shibu Sasidharan⁵
¹ Department of Paediatrics, 166 Military Hospital, Jammu, Jammu and Kashmir, India
² Department of Pediatrics, INHS Kalyani, Vishakhapatnam, Andhra Pradesh, India
³ Department of Pediatrics, Army Institute of Cardiothoracic Sciences, Pune, Maharashtra, India
⁴ Department of Psychiatry, Level III Hospital, Goma, DRC
⁵ Department of Anaesthesiology and Critical Care, Level III Hospital, Goma, DRC

Date of Submission	01-Apr-2021
Date of Decision	24-Jun-2021
Date of Acceptance	30-Jun-2021
Date of Web Publication	22-Dec-2021

Correspondence Address:
Shibu Sasidharan
Department of Anaesthesiology and Critical Care, Level III Hospital, Goma
DRC

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpai.jpai_5_21

Abstract

Background: Transient tachypnea of the newborn (TTNB) has been documented as the most common cause of neonatal respiratory distress, accounting for more than 40 percent of cases. Materials and Methods: This study was a prospective study on 75 patients (neonates who were born with TTNB) who underwent two-dimensional (2D) echocardiography (Echo) after tachypnea subsided. The controls (neonates who did not manifest tachypnea) were matched for birth weight, period of gestation, mode of delivery, and sex. Appropriate Chi-square tests were done for categorical variables, while Student's t-test was done for continuous variables. Results: Incidence of asymptomatic structural cardiac lesions detected by 2D Echo was significantly higher in neonates in the study group (n = 38; 50.66%) as compared to the control group (n = 7; 9.33%). This difference was statistically significant P < 0.0000002 (odds ratio 9.4586; 95% confidence interval 3.84–23.27). The most common cardiac lesion in both groups was atrial septal defect. Conclusion: The incidence of asymptomatic structural cardiac defects was found to be approximately five times higher in neonates manifesting TTNB (50.66% vs. 9.33%). Based on the findings of this study, screening for structural cardiac lesions by 2D echo is recommended in all neonates who manifest with TTNB.

Keywords: Atrial septal defect, cardiac lesions, fetal lung fluid, transient tachypnea of newborn

How to cite this article:
Dhillon GK, Narayan S, Ramamoorthy A, Dhillon HS, Sasidharan S. Association of asymptomatic structural cardiac defects in neonates with transient tachypnea at birth: A case-control study. J Pediatr Assoc India 2020;9:140-5

How to cite this URL:
Dhillon GK, Narayan S, Ramamoorthy A, Dhillon HS, Sasidharan S. Association of asymptomatic structural cardiac defects in neonates with transient tachypnea at birth: A case-control study. J Pediatr Assoc India [serial online] 2020 [cited 2023 Jun 3];9:140-5. Available from: http://www.jpai.in//text.asp?2020/9/4/140/333374

Introduction

The transition from fetal to extra-uterine life with removal of fluid from the airways, lung aeration, and onset of spontaneous breathing is one of the greatest physiological challenges that newborn encounters after birth.^[1],[2] Failure to remove fluid from the alveoli results in a functional reduction of alveolar surface area, insufficient gas exchange, and respiratory distress manifesting as tachypnea.^[3],[4] Transient tachypnea of newborn (TTNB) is described as “tachypnea within first few hours of birth associated with mild signs of respiratory distress including retractions, expiratory grunt, cyanosis and occasionally decreased oxygen saturation which is alleviated by minimal supplemental oxygen (FiO₂<0.4).”^[5] The initial clinical picture resolves completely by 24–72 h, hence the term transient.^[5] The most important pathophysiology behind TTNB is thought to be disruption or delay in clearance of fetal lung fluid.^[6] TTNB is associated with clinical findings such as tachypnea of usually more than 12 h duration commencing in the 1^st h after birth in the absence of sepsis/infection in the neonate with hyperinflation and evidence of perihilar edema in chest radiographs.^[7] Risk factors for TTNB include prematurity.^[8] birth asphyxia,^[9] male sex,^[10] cesarean delivery,^[11] multiparity,^[12] mothers with asthma,^[13] and diabetes.^[14] TTNB has been documented as the commonest cause of neonatal respiratory distress, constituting more than 40% of cases.^[15] A study involving 33,289 term deliveries revealed the prevalence of TTNB to be 5.7/1000 births.^[16] The potential complications of TTNB include a significantly increased risk of a wheezing disorder in childhood,^[17] childhood asthma,^[18] and respiratory failure in some newborns.^[19]

There is no literature addressing the incidence of structural heart lesions in neonates with TTNB. A pilot study was done in this very tertiary care hospital and it revealed the incidence of asymptomatic structural cardiac lesions to be 44% in newborns with TTNB, compared to 14% in matched controls.^[20] The present study was conducted at the same center with a larger sample size to validate the above pilot study.

Materials and Methods

Study design

Prospective study was done at a tertiary care hospital over 2 years (January 2015–December 2016). The study group comprised neonates with TTNB fulfilling criteria while the control group had neonates without TTNB matched for birth weight, gestational age, sex, and mode of delivery.

Inclusion criteria

All newborns of gestation age ≥34 completed weeks having transient tachypnea after birth (defined as the respiratory rate of ≥60/min for ≥6 h with or without features of respiratory distress in the form of retractions, expiratory grunt, and cyanosis).

Exclusion criteria

Preterm <34 weeks of period of gestation or any neonate with respiratory distress syndrome due to surfactant deficiency as determined by clinical profile, chest radiograph and need for exogenous surfactant
Pneumonia/sepsis
Pulmonary hypertension
Meconium aspiration syndrome
Cyanotic congenital heart disease or symptomatic congenital heart disease
Congenital diaphragmatic hernia/congenital cystic adenomatoid malformations
Neonate with central nervous system depression due to asphyxia/hypoxic insults/metabolic disturbances
Neonate with congenital anomalies
Any newborn fulfilling inclusion criteria but whose parents deny the consent for inclusion in the study.

Controls

All neonates with TTNB were matched for birth weight, period of gestation, mode of delivery, and sex with suitable controls (neonates who did not manifest tachypnea). Controls were also chosen serially; i.e., the first neonate born after a study subject, whose above-mentioned parameters matched a study subject, was enrolled as control after obtaining parental consent.

Methodology

Informed consent was obtained from the parents of the study group as well as the controls. Information regarding gestational age, body weight, clinical manifestations, risk factors as, maternal diseases (diabetes mellitus, asthma, hypertension, and anemia), maternal drug history (dexamethasone), lines of treatment, complications, etc., was obtained by medical history and records. No mother in the study or control group had a history of diabetes mellitus or bronchial asthma.

Complete clinical examination was done with special emphasis on the cardiovascular and neurological examination. Diagnosis of TTNB was made by the treating pediatrician based on history, clinical manifestations (early onset of tachypnea resolving spontaneously or responding to oxygen within 48–72 h), and exclusion of other causes of respiratory distress). Supportive radiographic findings on chest X-ray (increased pulmonary vascular markings, over aeration of the lungs) were also taken into consideration. All neonates were sampled for complete blood count, micro-erythrocyte sedimentation rate, C-reactive protein, and blood culture. All those who had positive C-reactive protein and/or positive blood culture results were excluded from the final analysis. None of the neonates in the study group had features of sepsis or any other systemic illnesses during the disease nor did any neonate in the study group receive antibiotics. Within the first 10 days of life, all study subjects, as well as controls, underwent a two-dimensional (2D) Echocardiographic examination. In study subjects, 2D Echocardiography (Echo) was done after the TTNB had resolved. The same Cardiologist, who was blinded to clinical details of the subjects, did 2D Echo for all neonates. 2D Echo was done using a pediatric transducer (4–7.5 MHz; PA 122E on Esaote My Lab 30 Gold). Standard transthoracic views including parasternal long axis, short axis, apical five-chamber, suprasternal, subcostal, and high parasternal were used. Persistent foramen ovale was diagnosed when there was an inter-atrial communication of <2 mm diameter with a flap-like opening with the bi-directional flow and without any evidence of right ventricular volume overload. All other structural lesions were diagnosed as per standard norms. Out of 75 cases, only one patient (1.3%) required nasal CPAP for 24 h, whereas other study subjects did not require any form of respiratory support other than supplemental oxygen. All neonates recovered fully and were discharged home on breastfeeds.

Sample size

Based on a previously done smaller study (n = 36) in the same institution, sample size was calculated. Using a two-sided confidence level of 95% and power of 80% with a 1:1 ratio of cases to controls, the sample size calculated by Epi Info software (version 7 CDC Atlanta) was 42 each of cases and controls. However, during the study period, 75 neonates with TTNB were included along with matched controls and data from these neonates analyzed.

Ethical clearance

Approval for the study was obtained from the institutional ethics committee (parental consent has already been mentioned).

Analysis

All data were analyzed using statistical software (Epi Info™ version 7.0, CDC, Atlanta). Appropriate Chi-square tests were done for categorical variables, while Student's t-test was done for continuous variables. All P values were two-tailed.

Results and Observations

Comparison of standard variables in the study versus control group

Transient tachypnea of newborn and mode of delivery

Out of 75 patients in study group, 53 (70%) were born vaginally whereas 22 (30%) were born by lower segment cesarean section (LSCS) [Table 1]. Out of 53 babies born by vaginal route, maximum 33 (62%) were born via spontaneous delivery and 20 (38%) required assisted delivery in form of forceps or vacuum. The overall risk of TTNB based on mode of delivery was as follows: Spontaneous vaginal delivery (44%) > emergency LSCS (24%) >vacuum (21%) > Forceps (0.5%) = Elective LSCS (0.5%).

Table 1: Comparison of standard variables in study versus control group

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Transient tachypnea of newborn and sex

Of the 75 study participants, 50 (66.6%) were male, and 25 (33.33%) females [Table 1]. The matched control group also had 50 males and 25 females. The male-to-female ratio was 2:1.

Transient tachypnea of newborn and birth weight

Out of 75 study participants, 13.3% (n = 10) were low birth weight (birth weight <2500 g), whereas 86.7% (n = 65) study participantsweighed between 2500 g and 4500 g. All neonates were appropriate for age. The birth weight of the study group was matched with controls, in which (58.6%; n = 44) had birth weights between 2500 g and 3499 g. Though the mean birth weight of neonates in the control group was 61.78 g higher than that of neonates in the study group, it was not statistically significant [Table 1].

Transient tachypnea of newborn and period of gestation

Of the study subjects, only five (6.66%) were near-term (born between 34 weeks and 37 weeks) and seventy (93.33%) were term neonates. Since the control group was matched for gestational age, the distribution of the control group in terms of gestational age was similar to that of study participants [Table 1]. It was observed that the incidence of TTNB was maximum (36%; n = 27) at 39 weeks. The incidence at 37, 38, 39, and 40 weeks was 13%, 21%, 36%, and 22.6%, respectively. The incidence of TTNB in late preterms (those born between 34 and 37 weeks) was 6.6% (n = 5).

Incidence of asymptomatic structural cardiac defects

The incidence of structural cardiac lesions detected by 2D Echo was significantly higher in neonates in the study group (n = 38; 50.66%) as compared to the control group (n = 7; 9.33%) [Table 1]. This difference was statistically significant with the two-tailed P < 0.0000002 (odds ratio 9.4586; 95% confidence interval [CI] 3.84–23.27). The incidence of asymptomatic structural cardiac defects was found to be approximately five times higher in neonates manifesting TTNB (50.66% vs. 9.33%).

Comparison of variables within the study group (transient tachypnea of newborn plus cardiac defects)

Association of cardiac defects with mode of delivery

Out of 53 neonates delivered by vaginal delivery, 29 (54%) had cardiac defects while out of 22 neonates delivered by LSCS, 9 (40%) had cardiac defects [Table 2]. TTNB and also cardiac defects were observed to be more common in babies born by vaginal delivery, though this difference was not statistically significant (two-tailed Fisher exact P = 0.318; odds ratio 1.745; 95% CI 0.637–4.779).

Table 2: Comparison of variables within the study group

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Association of cardiac defects with sex of newborns

Out of 75 study participantswho manifested TTNB, 50 were males and 25 were female. Out of 50 males, 25 neonates (50%) had cardiac defects and 13 (52%) out of 25 females had cardiac defects [Table 2]. The difference in the incidence of structural cardiac lesions by sex was not statistically significant (two tailed Fisher exact P = 0.398; odds ratio 2.564; 95% CI 0.497–13.22). The incidence of structural heart diseases in the control group (those without TTNB) was (n = 7) 9.33% (3 males and 4 females).

Association of cardiac defects with the duration of tachypnea

The mean duration of tachypnea in the study group (n = 75) was 47.28 h (standard deviation (s.d) = 24.44 h, median = 48 h, range = 6.0–96.0 h). The duration of tachypnea in neonates with structural cardiac lesions (n = 38) was 51.57 h (s.d = 24.47 h, median = 48 h, range = 24.0–96.0 h) while for those without cardiac lesions (n = 37) was 45.00 h (s.d = 21.95 h, median = 48 h, range = 6.0–96.0). Though neonates with cardiac lesions had longer mean duration of tachypnea, this difference was not statistically significant (Student's t-test, P = 0.2256).

Nature of cardiac defects detected in the two groups

The commonest cardiac lesion in both groups was atrial septal defect (ASD), detected in 26 (68%) in the study group and in 4 (58%) in the control group. The largest ASD was 7.3 mm OS ASD with left to right shunt. In the study group, four neonates had patent ductus arteriosus (PDA) (10%), one neonate had ASD with a PDA and another had a ventricular septal defect (VSD) (VSD with ASD and PDA) [Table 3].

Table 3: Nature of structural cardiac lesions detected in the two groups

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Discussion

This study was done to explore the association of asymptomatic structural cardiac defects with TTNB at birth. The incidence of TTNB in study group was observed to be 70% (n = 53) in vaginal deliveries and 30% in LSCS (n = 22) [Table 1]. This finding is not in agreement with multiple other studies where cesarean delivery has been found to increase the complexities of respiratory problems.^[21],[22] This difference can be attributed to a small sample size of 75 neonates. Out of 53 vaginal deliveries, vacuum delivery (21%) had higher risk of developing TTNB than forceps (0.5%) delivery.

Out of 22 study participantsborn by cesarean section, 0.5% (n = 4) were elective cesarean after trial of labor, whereas 24% (n = 18) were emergency section (without any trial of labor). Higher incidence of TTNB was seen in emergency LSCS compared to elective LSCS with the trial of labor (24% vs. 0.5%). This finding is in consonance with Morrison et al.^[23] and Cohen and Carson^[24] where the incidence of respiratory morbidity was found to be significantly higher for subjects delivered by emergency LSCS before the onset of labor. This finding of the current study strengthens the theory of protective effects of labor against TTNB^[25] and is clinically relevant, as it affirms the importance of trial of labor even in the case of elective cesarean section.

Subjects with TTNB had male predominance; 66.6% (50) were males and 33% (25) were females (male: female 2:1) [Table 1]. This finding is similar to multiple other studies.^[12],[26] This can be attributed to the inherent difference between males and females in the growth and maturation of lungs and increased incidence of surfactant deficiency in males.^[27]

The incidence of TTNB was maximum at 39 weeks (36%, n = 27) and week wise incidence at 37, 38.39, and 40 weeks was 13%, 21%, 36%, and 22.6% respectively. The decreased incidence of TTNB at higher gestation can be explained by changes in the lung vasculature, increase in the caliber of small pulmonary blood vessels (up to 40 times) in the 3^rd trimester, and changes in the epithelial sodium channels with increased ability to clear fetal lung fluid at term and with labor.^[28] This finding of the current study did not match with other studies^[29] where respiratory dysfunction was inversely related to the period of gestation. This disparity can be attributed to the fact that preterm newborns were administered antenatal steroids, which is a standard of care in our institution.

The incidence of TTNB was maximum (58.6%) in neonates having birth weights of 2500–3499 g and decreased with increase in birth weight. This finding is in agreement with a study by Hameed et al.^[30] in which incidence of TTNB decreased with higher birth weight. Only 10 neonates being low birth weight in our study, correlation between low birth weight and incidence of TTNB could not be made. However, the incidence of TTNB in low birth weight (1500–2499 g) was higher (13.3%) than in neonates weighing more than 4500 g (1.3%). Preterm babies (<34 weeks) were excluded from the study. Only 5 (6.6%) babies out of 75 in each group were late preterms (34–37 weeks). Since the number of late preterms was too small, no meaningful conclusions could be derived regarding susceptibility of this select group to TTNB.

Structural cardiac lesions were found to be five times more (50.66% vs. 9%) in neonates with TTNB compared to matched controls in the current study [Table 1]. It is worth emphasizing that the duration of tachypnea in neonates with structural cardiac lesions was not significantly different from that in neonates without cardiac lesions. These findings affirm the observations of a pilot study conducted by Narayan et al.^[20] in the same center. The existing literature on TTNB has mainly reported abnormal cardiac hemodynamic functions in neonates with TTNB and virtually no literature could be found addressing the incidence of structural heart lesions.^[31],[32] Cardiac dynamics during TTNB were not studied in the current study to eliminate observer bias of the Cardiologist performing the examination. Therefore, echo was done after the TTNB had subsided in study subjects.

The most common cardiac lesion in both groups was ASD, detected in 26 (68%) subjects in the study group [Table 3].

The strengths of this study include having a well-matched control group and the blinding of the cardiologist to the presence or absence of tachypnea. A drawback of this study is cardiac dynamics and the effect of these cardiac lesions on TTNB was not studied.

Conclusion

This study brings to the fore two important observations:

Neonates with TTNB are more likely to have asymptomatic structural cardiac lesions
Neonates with TTNB, the duration of tachypnoea in those with asymptomatic structural heart lesions is not different from those without such cardiac lesions.

All neonates with asymptomatic structural cardiac defects and TTNB made full recovery. Our findings suggest that these cardiac lesions did not contribute to TTNB since the difference in duration of tachypnea in both the groups (with and without structural cardiac lesions) was not significantly different. All neonates diagnosed with structural cardiac defects are under regular follow-up. Based on the findings of this study, screening for structural cardiac lesions by 2D Echo is recommended in all neonates who manifest with TTNB.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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