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Year : 2021  |  Volume : 10  |  Issue : 4  |  Page : 220-226

The effect of antenatal betamethasone on prevention of neonatal respiratory distress syndrome before elective cesarean section at term

Department of Obstetrics and Gynecology, Tabriz University of Medical Science, Tabriz, Iran

Date of Submission27-Apr-2021
Date of Decision10-Aug-2021
Date of Acceptance13-Aug-2021
Date of Web Publication24-Sep-2021

Correspondence Address:
Farnaz Sahaf
Department of Obstetric and Gynecology, Tabriz University of Medical Science, Tabriz
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.jcn_53_21

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Background: Respiratory distress syndrome (RDS) is an important respiratory disease possibly caused by surfactant deficiency in infants and has a heavy financial burden on the country's health system. The purpose of the present study was to evaluate the relationship between RDS in neonates who were born by elective cesarean at term with and without corticosteroids. Materials and Methods: This randomized clinical trial study was performed on all mothers who delivered by elective cesarean section at Alzahra and Taleghani Hospital with a Pregnancy age of more than 37 weeks. After considering exclusion criteria, the patients were randomly divided into either betamethasone (IM injection of 12 mg daily for two doses) or the control group. The comparison of these two groups was in RDS, hospitalization in the neonatal ward, or admission to newborn intensive care unit (NICU). Results: One hundred and sixty patients participated in the study. Fifty percentage (n = 80) of them received betamethasone and 50% did not. Of all, 160 neonates, 73.8% in Group 1 and 82.5 of the Group 2 had a 1st-min Apgar score of 9.9–9.10. Significant differences were observed in neonatal Apgar score in two groups (P < 0.05). RDS was found in 11 (6.87%) neonates born from both groups. The hospitalization of neonatal in intensive care units and the time of hospitalization of infants in the betamethasone group were less than the control group and statistically significant (P < 0.05). No cases of necrotizing enterocolitis and neonatal sepsis were observed. Conclusion: The results of the present study represented that giving betamethasone to mothers with programmed elective cesarean at term beseem to have a beneficial effect on RDS, NICU admission, and hospitalization. More studies with a larger sample size including the effects of other steroids are recommended.

Keywords: Betamethasone, cesarean section, elective, respiratory distress syndrome

How to cite this article:
Sahaf F, Zakariya NA. The effect of antenatal betamethasone on prevention of neonatal respiratory distress syndrome before elective cesarean section at term. J Clin Neonatol 2021;10:220-6

How to cite this URL:
Sahaf F, Zakariya NA. The effect of antenatal betamethasone on prevention of neonatal respiratory distress syndrome before elective cesarean section at term. J Clin Neonatol [serial online] 2021 [cited 2022 Dec 6];10:220-6. Available from: https://www.jcnonweb.com/text.asp?2021/10/4/220/326611

  Introduction Top

Respiratory distress syndrome (RDS) is an important frequent respiratory disease possibly caused by surfactant deficiency in neonates, and its global prevalence rate estimates for approximately 1% of all deliveries.[1],[2] Research studies showed that, in the United States, 80–60 thousand infants are born with RDS each year, of which about 6–12 thousand die.[3],[4],[5] RDS happened not only in preterm neonates but also in term neonates delivered by cesarean section (CS). On the other hand, one of the world's concerns is cesarean delivery as another method of termination of pregnancy.[6] According to previous studies, in Asia, Turkey (47.9%) and Iran (47.5%) have the uttermost rates of cesarean section, respectively.[7] In the last three decades, the prevalence of cesarean section in Iranian women has permanently increased. The statistical analysis of the survey demonstrated that 35% of Iranian babies were delivered by cesarean,[8] and this rate significantly increased due to various reasons from 37% in 1991 to 52% in 2013 and above 90% in private hospitals.[9] The complications of elective cesarean section at term for babies have not received much attention.

Signs of RDS in newborn infants, owing to the reactions to decreased pulmonary activity, are mostly appearing after birth or within 4 h and are characterized by abnormally rapid breathing or tachypnea, grunting, abnormal respiratory sounds nasal flaring, intercostal retraction, pulmonary edema, cyanosis in room air, decline urination within 24–48 h after birth, and bilateral and relatively symmetric diffuse ground-glass lungs with low volumes and a bell-shaped thorax.[10]

In recent years, for treatment or prevention of RDS, many strategies and therapies have been developed and tested including oxygen therapy or mechanical ventilation, the applying of surfactants or Vitamin D to infants with RDS, the acceleration of fetal lung maturation by administering steroids to the mother.[11],[12]

The actions of corticosteroids relevant to RDS are their anti-inflammatory actions and their remarkable role in the lung's maturity during gestation by producing surfactant and sodium channel functions improvement. The number of studies showed that giving antenatal corticosteroid to the woman at <35-week gestation are effective at reducing the incidence of RDS.[13],[14],[15] However, there is small evidence on the effect of applying corticosteroid on RDS in the 37th week of gestation or later.

Due to the prevalence of RDS in infants, the heavy financial burden on the country's health system, and also because of different results in different studies, the present study aimed to investigate the relationship between RDS in neonates were born by elective cesarean at term with and without corticosteroids cover and assess the factors that influence the risk of RDS in newborn infants.

  Materials and Methods Top

This randomized clinical trial was carried out in Taleghani Medical Clinic and Alzahra hospital of Tabriz University of Medical Sciences in Tabriz in 2019–2020.

All the cases with single pregnancies who were candidates for planned elective CS with 37-week gestation (term) were entered into the study.

Ethical approval for this study was obtained from the Medical and Research Ethics Committee at the College of Medicine and Health Sciences, Tabriz University of Medical Sciences, Iran (the registration code: IR.TBZMED.REC.1398.071).

A total of 160 pregnant women were entered in the study. Our inclusion criteria were women with a single pregnancy and with a pregnancy age of more than 37 weeks, without medical disorders and problems during pregnancy. Women with anomalous fetuses and complications such as preeclampsia and high blood pressure, diabetes mellitus, vaginal bleeding, known fetal anomaly, and growth-restricted fetuses, drug addicts, preterm delivery, delivery after 39 weeks gestation, multiple gestations, and Women who refused to take part in the study were excluded from the study.

The real-time termination of pregnancy for all referring women was determined by midwifery indications such as the membranes rupture and onset of labor pain. Before the study begins, the study processes and the goals of the research were explained to all parents and they signed written informed consent.

According to the order of women enrolling into the study, they were randomly divided into either betamethasone group (IM injection of 12 mg of betamethasone in two doses based on the time of cesarean section, the patient was injected 48 h before delivery) or control group (routine treatment).

The data were accumulated by designed questionnaires from the delivery ward and newborn intensive care unit (NICU). Before the termination of gestation, nurses, midwifery, and pediatric residents were asked to assist in gathering information. Then, the cesarean section was performed routinely.

Maternal demographic and medical data such as age, education level, body mass index (BMI), glucose, and gestational age at delivery were collected before, during, and after delivery. All the neonatal data and possible disorders were recorded including gender, birth weight, Apgar score, infant heart and breathing rate, admission to NICU, diagnosis of RDS, TTN, other complications, medical intervention, the need for mechanical ventilation, and the need ventilator support. Criteria for RDS based on Fanaroff and Oxford textbooks were (1) beginning of respiratory distress in the operating room after surgery or within 6 h after birth, (2) an arterial oxygen tension (Pao2) <50 mm Hg and central cyanosis in room air, a requirement for supplemental oxygen to maintain Pao2 more than 50 mm Hg, or a requirement for supplemental oxygen to maintain SPo2 over 90%, (3) Chest X-rays (CXR) view: uniform reticulogranular pattern to lung fields with or without low lung volumes within the 1st 24 h of life and air bronchograms and white lung in severe cases, and (4) role out other respiratory distress causes such as TTN and MAS based on CXR and signs.[14],[16] Diagnosis was based on the opinion of the neonatologist based on criteria.

Data were analyzed using SPSS. (2015). SPSS. (Chicago, IL: IBM SPSS, Inc.). Descriptive statistics were used to analyze data. We used Chi-square and independent sample t-test to determine the relationship between independent and dependent categorical variables. A P ≤ 0.050 was considered statistically significant.

  Results Top

One hundred and sixty pregnant women have been participated in the study and were divided into two groups of women who received betamethasone (Group 1) (80 patients) and women without betamethasone administration (Group 2) (80 patients). As demonstrated in [Table 1], the average age of the studied women in the betamethasone and control group was 32.71 ± 6 and 31.71 ± 7 years, respectively, and the mean BMI of the studied women in betamethasone and control group was 26.06 ± 2.1 kg/m2 and 27.16 ± 1.4 kg/m2, respectively. Nearly 65.7% of women had high school or higher degrees and 78.9% of them were housewives. Individual characteristics of mothers in the two groups were not significantly different in age, occupation, BMI, and education (P > 0.05).
Table 1: Individual characteristics of mothers participating in the study (n=80) and control (n=80) group

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The baseline characteristics of participating women and neonates are shown in [Table 2]. Of all, 21 women (13.12%) gave birth with CS at the 37th week, 95 cases (59.37%) gave birth at the 38th week, and 44 women (27.5%) gave birth at the 39th week. Mean gestational age was 38.2 ± 1 and 38.0 ± 0.8 weeks in Groups 1 and 2, respectively. There was no significant difference between the betamethasone and control group in terms of gestational age, parity, blood pressure and fasting blood sugar, and maternal heart rate (P > 0.05).
Table 2: Comparison of women and neonates' characteristics between betamethasone (n=80) and control groups (n=80)

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Group 1 consisted of 33 boys (41.3%) and 47 girls (58.7%), and Group 2 consisted of 42 boys (52.5%) and 38 girls (47.5%). Following analysis of gender between two groups was not observed no significant differences (P = 102 using Chi-square). The mean (standard deviation) of neonates' weight in Groups 1 and 2 was 3056 + 130 g and 3031 ± 213 g, respectively. Analysis of infants' height, weight, heart rate, and respiratory rate between two groups showed no significant differences (P = 0.367, 0.10, 0.06, and 0.24, respectively).

Of all, 160 neonates, 73.8% in Group 1 and 82.5 of the Group 2 had a 1st-min Apgar score of 9.9–9.10. Significant differences were observed in neonatal Apgar score in two groups (P < 0.05).

Respiratory distress was diagnosed in 11 (6.87%) neonates delivered from both groups. Two cases (%2.5) belong to Group 1, who were discharged with TTN diagnosis after 1 day of follow-up and oxygen therapy under the hood, and nine cases (%11.25) belong to Group 2 with RDS and the relative risk was calculated to be 4.5 (P < 0.05) [Table 3]. Amniotic fluid in these 11 cases was clear.
Table 3: Comparison of the neonatal respiratory outcomes and their relative risk in betamethasone (n=80) and control groups (n=80)

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The need for hospitalization in Group 1 and 2 was determined as 2 cases (2.5%) and 9 cases (11.25%), respectively, and their relative risk was calculated to be 9, which differences were statistically significant (P < 0.05). This difference was also observed about the need for respiratory support. No cases of necrotizing enterocolitis and neonatal sepsis were observed [Table 3].

In the second group (without betamethasone administration), based on neonatologist opinion and criteria, nine infants had RDS. Two of them had tachypnea, tachycardia, and subcostal retraction that admitted to the neonatal intensive care unit NICU and their CXR showed RDS; they were severe RDS and treated with nasal continuous positive airway pressure (NCPAP), surfactant and high-flow nasal cannula, and their CXRs were improved, and after 3 days, they were transferred to the neonatal ward. Other seven with reticulogranular pattern in CXR and mild RDS underwent NCPAP, four infants were hospitalized for 3 days, and three infants were hospitalized for 2 days in NICU. The infants were hospitalized in the neonatal ward for another day and then discharged in good general condition. Blood culture of all patients was negative.

In the analysis, by logistic regression [Table 4], the variable of RDS was considered as the dependent variable, and the variables of betamethasone group, gestational age, birth weight, Apgar, and the presence of respiratory distress were placed as independent variables in the model. Birth weight (P = 0.001), betamethasone group (P = 0.016), and respiratory distress (P < 0.01) remained in the model. Analysis showed that, after controlling birth weight and the presence of distress during childbirth, the effect of the betamethasone on reducing respiratory distress was statistically significant (r2 = 0.32).
Table 4: Logistics regression analysis results

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  Discussion Top

RDS is a well-known neonatal complication in babies after elective cesarean section and possibly caused by the surfactant deficiency; the possible reasons for RDS in full-term neonates are (1) acquired infection, (2) elective cesarean section that has been suggested surfactant deficiency was the main reason of RDS in these cases, (3) asphyxia, (4) pulmonary hemorrhage, (5) inherited disorders of surfactant metabolism, so many interventions and treatment studied and introduced in the last decades.[17],[18],[19] Administration of corticosteroids such as betamethasone is one of these interventions that enhances the production of surfactants and has a well-reported effect in reducing respiratory distress.[20] In the present study, we investigated and compared the effect of the administration of betamethasone on RDS in the 37th week of gestation or more.

Based on the findings of the present study, the prevalence of neonatal RDS in the intervention group, whose mothers received betamethasone, was less than the control group. Analysis proved that the prevalence of RDS was 2.5% in the intervention group. While in the control group, the prevalence was 11.25% (4.5 times). There was clear evidence about the maternal administration of corticosteroids for preterm birth and improvement of neonatal complications and respiratory morbidity[18],[21] but giving it to term birth is controversial. Hence, the results of a study showed that administering antenatal corticosteroids at term before cesarean section and before 39-week gestation is not recommended,[22] and the results of a study by Nihal Alrahimi[23] did not show the positive effect of antenatal betamethasone administration in reduction of respiratory morbidities because of the little sample size, but to the contrary, in other studies, it is suggested to plan to administer corticosteroid in the elective cesarean section at 39 weeks wherein the risk of RDS and respiratory morbidity could be decreased.[18],[23] In a study by Sotiriadis, in 2018, included four trials, and compared effects of betamethasone or dexamethasone treatment without term elective cesarean section. In the mentioned study, they proved some beneficial effects of steroids treatment, but they concluded that, to discover the effect of corticosteroids on the improvement of respiratory complications, further high-quality studies with more sample size should be studied.[24]

In our study, the need for respiratory support was also significantly different between the two groups and the requirement for respiratory support was less in the intervention group, which is due to the acceleration of lung maturity and reducing pulmonary problems in the neonates of the intervention group. These findings are consistent with the findings of other studies.[25],[26]

The finding of the present study also showed that, by controlling possible confounding factors such as gestational age, birth weight, and asphyxia during labor, betamethasone still had a statistically significant effect on the prevention of this syndrome, and the control group was 4.6 times more likely to suffer from the RDS. In our study, similar to other studies,[26],[27] low birth weight was significantly associated with RDS and the incidence of this syndrome in children under 2500 g was about 5.3 times higher than infants weighing more than 2500 g. This increase was also very high in children with asphyxia for every reason.

The results of our study were consistent and in line with a study that showed a significant difference in the incidence of neonatal RDS in the intervention groups (betamethasone injection in pregnant women) and the control group.[18],[28]

In this study, there were no cases of necrotizing enterocolitis and intraventricular hemorrhage. It should be mentioned that the risk of these problems has an inverse relationship with uterus age and birth weight so that smaller and premature babies are more susceptible to these complications. Considering that the neonates studied in our study were 37–39 weeks and there were no low-birth-weight infants (<2000 g), so the incidence of these complications was reduced.

In the present study, the number of hospital days has a significant statistical difference in the two groups and the number of NICU admitted and hospitalized neonates was significantly less in the betamethasone group than in the control group. Also considering that the need for respiratory support was lower in the betamethasone group; betamethasone may reduce hospitalization days, this is along a study conducted in Tehran, Iran by Kashanian et al.[29],[30]

In the betamethasone group, Apgar scores were higher and better; the need for resuscitation and the incidence of RDS was lower than in the other group, indicating the effect of betamethasone on neonatal cardiopulmonary stabilization, and an enhancement in the general condition of infants and similar studies have shown similar results.[31],[32]

  Conclusion Top

The finding of this study demonstrated that giving betamethasone to mothers with programmed elective cesarean at term beseem to have an advantageous effect on neonatal RDS, NICU admission, and hospitalization. More studies with larger sample size including the effects of other steroids are recommended.


Dr. Sadollah Yeghanedoost (Assistant Professor of Neonatal-Perinatal Medicine Department of Pediatrics, School of Medicine Children Medi cal Research & Training Hospital Tabriz University of Medical Sciences) is especially thanked and appreciated for helping us in neonatal part. We also thank Maryam Rostami (Tehran university of medical science) for her help in the final editing of this article.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4]


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