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Revisiting the use of antenatal corticosteroids for late preterm and early term infants: An observational analytical study

 Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India

Date of Submission15-Sep-2022
Date of Decision21-Nov-2022
Date of Acceptance22-Nov-2022
Date of Web Publication02-Mar-2023

Correspondence Address:
Femitha Pournami,
Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram - 695 029, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrsm.jcrsm_75_22


Background: Guidelines from prominent policymakers on the use of antenatal steroids (ANS) in “late preterm deliveries and early term casearian deliveries” (LET) are nonuniform. This descriptive study compared LET infants born during two-time epochs: Retrospective: ANS exposed (ANSE) (when institute practice was to administer ANS to all LET mothers), and prospective – ANS unexposed (ANSU) (after the policy was revised in May 2021).
Methodology: All antenatal mothers of anticipated late-preterm and early-term cesarean deliveries were being administered ANS before May 2021. Following the revision of hospital policy, this practice was discontinued. Comparative analysis for respiratory morbidity (RM) and other clinically relevant outcomes were conducted in infants born during two-time epochs (ANSE vs. ANSU)
Results: Among 379 included infants, those with RMs were comparable between groups: 33 (17.5%) in ANSE; 31 (16.4%) in ANSU – Odds ratio (OR) 1.08; 95% confidence interval (CI) (0.61–1.92), P = 0.78. No difference was noted in hypoglycemia events: 23 (12.2%) in ANSE; 22 (11.6%) in ANSU, OR = 1.05 95% CI (0.56–1.96), P = 0.87.
Conclusion: ANS in LET did not seem to reduce the risk of RM. It may be appropriate to audit individual unit practices and relevant outcomes before blanket recommendations are made.

Keywords: Antenatal steroids, early term, late preterm, respiratory distress

How to cite this URL:
Rugmini SS, Pournami F, Prithvi AK, Nandakumar A, Prabhakar J, Jain N. Revisiting the use of antenatal corticosteroids for late preterm and early term infants: An observational analytical study. J Curr Res Sci Med [Epub ahead of print] [cited 2023 Mar 31]. Available from: https://www.jcrsmed.org/preprintarticle.asp?id=370926

  Introduction Top

Indisputable evidence supports the use of antenatal steroids (ANS) to improve neonatal outcomes for deliveries between 24 and 34 weeks gestation.[1] A large body of literature also proves that late preterm; and to a lesser extent, early-term infants are at risk of respiratory illnesses and other short-term morbidities. This group also requires close follow-up for long-term concerns.[2] Respiratory distress syndrome and transient tachypnea of the newborn are the two most common respiratory morbidities (RMs) in this group of infants. The biological basis for the use of ANS lies in its ability to facilitate surfactant production and improve lung fluid resorption.[3] Literature suggests that the benefits of giving antenatal corticosteroids may extend to late-preterm and early-term infants LET as well, but with high numbers needed to treat.[4] Furthermore, major guidelines do not seem to agree on the use of ANS in LET.[1],[5],[6],[7] Moreover, one cannot be complacent about the risks associated with ANS use.

The obstetric–perinatal–neonatal departments of our multispecialty referral hospital were previously giving ANS to expectant mothers of LET (all late-preterm deliveries and early-term cesarean deliveries). A perinatology meeting held in this regard in May 2021 examined the scientific evidence available. A decision was made to withhold ANS for LET, as a uniform protocol. A systematic comparative analysis of the effects of this change was planned. Hence, the study investigated the possible short-term effects of ANS administration on RMs in infants.

  Materials and Methods Top

This before–after observational analytical study aimed to compare the proportion of infants with short-term outcomes: neonatal RMs and hypoglycemia; between two groups during two time epochs: Retrospective: ANS exposed (ANSE) – ANS given for expected delivery of late-preterm or early-term cesarean sections LET between November 2020 and April 2021; and perspective in the group unexposed to ANS (ANSU) between May and November 2021. Late-preterm pregnancies/infants were defined as those delivered between 34 weeks completion and 36 weeks, 6 days of gestation (i.e., 239–259 days after the 1st day of the last menstrual period).[8] Early-term infants are those born between 37 completed and 38 weeks, 6 days gestation.

Literature suggests wide variation in respiratory outcomes with ANS use in this gestational age group.[9] Therefore, for the purpose of sample size calculation, we assumed that there might be an expected increase in the proportion of infants with RM from 10% (in the retrospective cohort) to 20% (in the prospective cohort). For a confidence level of 95% and 80% power, we planned to include 189 infants in each group. Those mothers who were already on steroid therapy for other medical indications and those who had received a previous course of ANS before 34 weeks of gestation for threatened preterm delivery were excluded from the study.

The hospital has written policies for assessment of gestational age, timing of delivery, early initiation of breastfeeding, and dedicated lactation support teams who make at least daily twice postnatal rounds to ensure breastfeeding, monitoring, and therapy for respiratory illnesses. Maternal/perinatal details, birth information, and specifics of admission to the neonatal intensive care unit (NICU) (for early-term infants), and other outcomes were collected prospectively for the study group (ANSU). For the ANSE group, information was retrieved from electronic medical records.

We assessed as a primary outcome, the proportion of infants with RMs between the two groups; and as secondary outcomes, the proportion of infants with hypoglycemia (symptomatic and otherwise) between the two groups. The unit measures heel-stick glucose levels with a glucometer for a minimum of 48 h postnatal in LET. The monitoring is continued if sugar values are suboptimal (as defined below) after the institution of appropriate measures. The recording is then stopped if >24 h of glucose records are noted as normal. The proportion of infants in both groups with RM based on severity was also compared. Symptomatic hypoglycemia was defined as those with lethargy, poor feeding, seizures, and other signs of encephalopathy not explained by any other evident etiology; and blood glucose measurements (glucometer heel stick/venous whole blood values) <50 mg/dL; and asymptomatic hypoglycemia as well babies with blood glucose measurements (a) <24 h of life; <40 mg/dL (b) >24 h of life; <50 mg/dL. Mild RM was defined as clinical features of respiratory distress (mild tachypnea, mild retractions, no grunting, and no O2 requirement) requiring admission and monitoring in the NICU. Those with distress warranting noninvasive respiratory supports were classified as moderate RM, and those requiring invasive ventilatory support with or without surfactant administration were deemed as severe RM.

Data collected were analyzed using STATA Version 16. (Stata, StataCorp, USA). Continuous normally distributed variables were compared using Student's t-test, others by Mann–Whitney U-test, and categorical variables by Fisher's exact test. A P < 0.05 was considered statistically significant. We obtained the approval of the Institutional Committee for Human Ethics for Research (KIMS/IHEC/FE01/2021). Informed consent was obtained from parents in the prospective cohort. The protocol was registered in the Clinical Trials Registry of India (CTRI No. CTRI/2021/09/036810).

  Results Top

A total of 379 mother–baby dyads were studied [Figure 1]. In the retrospective group (ANSE), all mothers received the full regimen of ANS (four doses of 6 mg intramuscular dexamethasone administered every 12 h). No local or systemic adverse effects were recorded in the mothers due to corticosteroid treatment.
Figure 1: Study flow diagram

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The baseline characters are presented in [Table 1]. There were significantly more late-preterm births in the ANSU (prospective group). As a corollary, the median birth weights were significantly lower in the ANSU group. The COVID-19 situation led to a decrease in term low-risk deliveries in the initial phase of the pandemic. For the first several months of the pandemic, ours was one of the few hospitals that were accepting COVID-19-related admissions in the city. Families of low-risk pregnancies may have decided to deliver in “non-COVID” hospitals if there were no anticipated complications. Late preterm and other high-risk pregnancies continued their follow-up and delivery care here itself.
Table 1: Baseline characteristics comparison between groups

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Among the maternal morbidities, both groups had a similar number of mothers with pregnancy-induced hypertension. Incidentally, there were more women with gestational diabetes mellitus in the retrospective group.

Of all enrolled, 64 infants had “any RM.” The proportion of infants with RM was comparable between groups. No statistically significant difference was noted in hypoglycemia events [Table 2].
Table 2: Respiratory and hypoglycemia outcomes: Comparison between groups

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  Discussion Top

Our observational study compared late-preterm and early-term infants who were exposed to ANS versus those who were not, in two-time epochs. We found no statistically significant difference in the proportion of infants who developed RMs.

Scientific literature over the past several years has proven that late-preterm and early-term infants have higher risks of short-term illnesses than more mature neonates.[2] ANS before expected delivery between 34 and 36 weeks gestation may reduce the chances of RMs soon after birth.[2],[10] However, limitations in these studies include variations and shortcomings in their designs, nonuniform steroid regimens, etc.[10],[11] In a larger report that included 17 centers, steroids significantly reduced respiratory problems. But only 60% of participants completed the full course of steroids.[4] Other reports are contradictory and seem to not corroborate these findings.[9],[12],[13]

Current recommendations, therefore, stand divided on the use of ANS in this group. The American College of Obstetricians and Gynecologists recommends its use in pregnant women at risk of late-preterm birth, regardless of the mode of delivery. They do not recommend it in early-term cesarean deliveries.[1] On the other hand, the Royal College of Obstetricians and Gynaecologists, United Kingdom supports the use of ANS in planned cesarean deliveries performed before 39 completed weeks of gestation to reduce the risk of respiratory distress.[5] The WHO does not recommend ANS for either of these groups.[6] A recent Cochrane review reported a reduction in the risk of respiratory distress and admission into intensive care due to RM, but no difference in the need for invasive ventilation or mortality.[7]

Safety data remains sparse. We did not observe any significant difference in the risk of hypoglycemia between the exposed versus unexposed groups. Adverse effects have been documented, including impaired growth, neonatal hypoglycemia, and long-term effects such as poor school performance, increased vulnerability to stress-related conditions, and predisposition to metabolic illnesses.[3] In the early-preterm period, the benefits of antenatal corticosteroids are so pronounced that they outweigh the risks; contrary to the LET period where the small doubtful added benefit may be small and of questionable clinical value. Further work to assess the benefit and potential harm in late-preterm gestations and before early-term cesarean sections are required.[14]

Our study has some notable strengths. We designed a before–after observational study with a sizeable number of enrollments. Good interdepartmental communication and relationships between obstetrics, perinatology, and neonatology departments allowed a uniform change in practice. Inclusion of LET, without excluding gestational diabetes mellitus mothers/multifetal gestations is a pragmatic approach, as both these conditions are common in clinical practice. However, one group was retrospective with its inherent limitations of data retrieval. A noninferiority prospective study design would be an ideal one, but this would be ethically challenging. There were differences in the baseline characteristics (more late preterm in the prospective cohort). This, however, did not seem to affect the primary outcome in spite of the biological plausibility of higher expected RM in this cohort.

  Conclusion Top

There was no difference in the rate of RM or hypoglycemia between the group of late-preterm and early-term infants who received ANS as compared to those who did not.

As late-preterm and early-term deliveries form a high proportion of live-born neonates across all levels of care, there is an indisputable role for units to audit their practices regarding ANS usage in these groups. The results are likely to influence the use where benefits need to be weighed against risks. Till such time that the debate is conclusively resolved, it may be prudent to avoid iatrogenic late-preterm/early-term deliveries without justified indications.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Committee on Obstetric Practice. Committee opinion no. 713: Antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2017;130:e102-9.  Back to cited text no. 1
de la Huerga López A, Sendarrubias Alonso M, Jiménez Jiménez AP, Matías Del Pozo V, Álvarez Colomo C, Muñoz Moreno MF. Antenatal corticosteroids and incidence of neonatal respiratory distress after elective caesarean section in late preterm and term neonates. An Pediatr (Engl Ed) 2019;91:371-7.  Back to cited text no. 2
Haviv HR, Said J, Mol BW. The place of antenatal corticosteroids in late preterm and early term births. Semin Fetal Neonatal Med 2019;24:37-42.  Back to cited text no. 3
Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med 2016;374:1311-20.  Back to cited text no. 4
National Institute for Health and Care Excellence (NICE). Preterm Labour and Birth. NICE Guidance NG25. London: National Institute for Health and Care Excellence (NICE); 2015. Available from: http://www.nice.org.uk/guidance/ng25. [Last accessed on 2022 Sep 14].  Back to cited text no. 5
World Health Organization (WHO) Reproductive Health Library. WHO Recommendation on Antenatal Corticosteroid Therapy for Women at Risk of Preterm Birth from 24 Weeks to 34 Weeks of Gestation. Geneva: World Health Organization (WHO); 2015. p. 201  Back to cited text no. 6
Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JP, McGoldrick E. Corticosteroids for preventing neonatal respiratory morbidity after elective caesarean section at term. Cochrane Database Syst Rev 2018;8:CD006614.  Back to cited text no. 7
Stewart DL, Barfield WD. Committee on Fetus and Newborn; Updates on an At-Risk Population Late-Preterm and Early-Term Infants. United States of America: Pediatrics; 2019. p. 144.  Back to cited text no. 8
Ontela V, Dorairajan G, Bhat VB, Chinnakali P. Effect of antenatal steroids on respiratory morbidity of late preterm newborns: A randomized controlled trial. J Trop Pediatr 2018;64:531-8.  Back to cited text no. 9
Balci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest 2010;70:95-9.  Back to cited text no. 10
Attawattanakul N, Tansuspswatdikul P. Effect of antenatal dexamethasone on respiratory distress in late preterm infant: A randomized controlled trial. Thai J Obstet Gynecol 2015;23:25-33.  Back to cited text no. 11
Nada AM, Shafeek MM, El Maraghy MA, Nageeb AH, Salah El Din AS, Awad MH. RETRACTED: Antenatal corticosteroid administration before elective caesarean section at term to prevent neonatal respiratory morbidity: A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol 2016;199:88-91.  Back to cited text no. 12
Ahmed MR, Sayed Ahmed WA, Mohammed TY. Antenatal steroids at 37 weeks, does it reduce neonatal respiratory morbidity? A randomized trial. J Matern Fetal Neonatal Med 2015;28:1486-90.  Back to cited text no. 13
Busuulwa P, Groom K, Chappell LC, Shennan AH. The role of antenatal corticosteroids in improving neonatal outcomes. Obstet Gynaecol 2021;23:246-57.  Back to cited text no. 14


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  [Table 1], [Table 2]


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