Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(1): 20–27

Original Research

10.5455/NJPPP.2025.v15.i1.4

Impact of COVID-19 infection on pregnancy outcomes: A retrospective cohort study focusing on preterm and low-birth-weight pregnancies

Naladala Disha Chowdary^*, Chaitra Madanahalli Sridhar, Usha Kantharajanna, Srinivasulu Naidu, Shravanthi Venkatesh and Arjun Santosh Menon

Shri Atal Bihari Vajpayee Medical College and Research Institute, Bangalore, India

*Corresponding Author: Naladala Disha Chowdary. Shri Atal Bihari Vajpayee Medical College and Research Institute, Bangalore, India. Email: disharesearch2 [at] gmail.com

Submitted: 29/02/2024 Accepted: 15/12/2024 Published: 31/01/2025

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Abstract

Introduction: Viral infections pose significant risks to pregnant women and fetuses. Although the impact of many viruses on pregnancy has been well-documented, the specific effects of COVID-19 on gestational age and newborn development remain unclear. There is a need to investigate these relationships in an Indian context where data on COVID-19 and pregnancy outcomes are limited.

Aim: To determine the effect of COVID-19 infection on gestational age and birth weight in neonates born to COVID-19-positive mothers during the third trimester of gestation.

Materials and Methods: This retrospective cohort study used medical records collected from March 2020 to September 2022 at a tertiary hospital in Bengaluru. The data were analyzed in 2023. A total of 379 pregnant women aged 18–35 years were included in the study, out of which 325 were COVID-19 positive, while 54 were COVID-19 negative. In all the study subjects, comorbidities, gestational age, birth weight, and infection severity were recorded and analyzed. The chi-square test and Mood’s median test were used to compare COVID-19-positive pregnant women with COVID-19-negative pregnant women who delivered during the same time period.

Results: COVID-19 infected women had an average gestational age of 269.24 ± 16.11 days compared to noninfected women 270.33 ± 10.65 days with a p-value of 0.733. Approximately 13.84% (45) of COVID-19-positive women delivered their babies preterm. The study found that the average birth weight of babies born to COVID-19 infected mothers was 2.78 ± 0.53 kg compared to 2.81 ± 0.4 kg in noninfected mothers with a p-value of 0.637 and the birth weights in both groups were comparable to the average birth weight in India.

Conclusion: The study found that COVID-19 did not appear to increase the likelihood of adverse pregnancy outcomes, such as preterm delivery or low birth weight, in the studied population, suggesting that it does not pose a specific threat to the health of the mother or fetus.

Keywords: Viral infections, Gestational age, Intrauterine viral transmission, Growth restriction, Placental barrier.

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Introduction

Pregnancy is a vulnerable physiological state that increases the mother’s susceptibility to infection. These infections can also cross the placental barrier and pose a risk to the developing fetus (Mor et al., 2017).

Viral infections have become increasingly prevalent in recent times, causing significant disruption in society. Several viral infections, including hepatitis, herpes simplex, measles, rubella, and influenza, have proven to have adverse effects at various stages of pregnancy. The potential outcomes of these viral infections during pregnancy range from fetal growth restriction and premature delivery to stillbirth and higher maternal mortality rates (Waldorf and McAdams, 2013; Silasi et al., 2015).

Coronavirus, being structurally similar to influenza, could potentially influence pregnancy outcomes (Karimian and Delavar, 2020). The COVID-19 pandemic, which emerged in 2020, provided an opportunity to investigate its potential impact on various health outcomes. It was evident that pregnant women and the older adults were particularly vulnerable to COVID-19 infection (CDC, 2022; Li et al., 2020). [6] Although the duration of the pandemic was insufficient for a comprehensive study of all its effects, the specific impact of COVID-19 on pregnancy and childbirth has not been fully understood.

Physiological changes in the cardiorespiratory and immune systems during pregnancy can affect the body’s response to SARS-CoV-2 infection. Additionally, fetuses may be exposed to SARS-CoV-2 during crucial stages of development (Wastnedge et al., 2021).. While some studies have suggested a potential link between COVID-19 infection and low birth weight or preterm delivery (Beusekom, 2020; Wastnedge et al., 2021), others have found no evidence of intrauterine viral transmission or adverse effects on fetal growth or gestation (Parveen et al., 2022).

The nature of the association between COVID-19 and pregnancy outcomes remains unclear, and data involving patients who are pregnant with COVID-19 are limited. The findings on the relationship between COVID-19 and adverse pregnancy outcomes can inform obstetricians, policymakers, and healthcare workers about caregiving practices, vaccination strategies for pregnant women, and the allocation of medical resources.

The hypotheses for the study were given as follows.

Null Hypothesis (H0): There is no difference in the median gestational age at birth (preterm delivery) or the median birth weight between mothers with and without COVID-19.

Alternative Hypothesis (H1): There is a difference in either the median gestational age at birth (preterm delivery) or the median birth weight between mothers with and without COVID-19.

With this background, this study was conducted to determine the effect of COVID-19 infection on the gestational age and birth weight of neonates born to COVID-19-positive mothers during the third trimester of gestation.

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Materials and Methods

A retrospective cohort study was conducted at the Government H.S.I.S Gosha Hospital, Shivajinagar, Bengaluru, a dedicated COVID-19 maternity government hospital. This study analyzed medical records from March 1, 2020, to September 1, 2022. The data were analyzed in 2023. The Institutional Ethics Committee approval was obtained (IEC approval no.: SABVMCRI/IEC/RP/143/22-23).

Inclusion criteria

The study included pregnant women aged 18–35 years.

Exclusion criteria

Pregnant women who had pre-existing conditions, such as hypertension, diabetes, hypothyroidism, hyperthyroidism, asthma, epilepsy, or any other infections that could potentially affect the gestational age or development of a newborn, were excluded. These conditions were excluded due to their potential risks, including intrauterine growth restriction, fetal macrosomia, congenital malformations, preterm birth, stillbirth, increased perinatal complications, premature rupture of membranes, low birth weight, and neonatal hypoxia (Asthma in Pregnancy, 2008; Alexander et al., 2016; Luger and Kight, 2022; CDC, 2024).

Due to the hospital’s designation as a COVID-19 center during this period, 394 COVID-19 and 63 non-COVID-19 deliveries were documented. Of the 457 pregnant women screened, 379 met our inclusion and exclusion criteria and were included in the study, out of which 325 were positive for COVID-19 and 54 were negative.

Data collection

Medical records were retrieved from the Medical Records Section and categorized into COVID-19 and non-COVID-19 cases. The presence of COVID-19 was confirmed by reverse transcriptase-polymerase chain reaction as per institutional protocol based on ICMR and national guidelines [13].

Mother’s details, such as age, gravida, parity, number of abortions, mode of delivery, and COVID-19 severity based on COVID-19 symptoms such as fever, cough, abdominal pain, anorexia, chest tightness, diarrhea, dyspnea, expectoration, fatigue, headache, hemoptysis, myalgia, nausea or vomiting, SpO², ICU admission, need for ventilator/oxygen support, and duration of hospital stay, were noted (Alimohamadi et al., 2022). To isolate the impact of COVID-19, previous medical histories were examined to rule out other potential causes of low birth weight and preterm delivery.

Following birth, the 1- and 5-minute Apgar scores, COVID-19 status of the newborn, term of delivery, and birth weight of the newborns were recorded.

Babies born before 37 weeks of gestation were classified as preterm. Preterm babies were further categorized as follows.

• Extremely preterm: Born before 28 weeks.
• Very preterm: Born between 28 and 32 weeks.
• Moderate-to-late preterm: Born between 32 and 37 weeks.

Statistical analysis

The collected data were systematically tabulated and analyzed using Minitab Version 21.4 software. This statistical software enabled us to conduct a comprehensive analysis of the data, including descriptive statistics, hypothesis testing, and correlation analysis. The chi-square test was employed to test the hypothesis, and a p-value of <0.05 was considered significant.

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Results

In the present study, COVID-19 infected women had an average gestational age of 269.24 ± 16.11 days compared to noninfected women 270.33 ± 10.65 days.

The average birth weight of babies born to COVID-19 infected mothers was 2.78 ± 0.53 kg compared to 2.81 ± 0.4 kg in noninfected mothers (p=0.637) (Figs. 2 and 3).

In Table 1/Figure 1, the p-value is >0.05, so Ho is accepted. COVID-19 had no significant impact on birth weight.

As shown in Table 2, p-value >0.05 indicates that COVID-19 had no significant impact on gestational age.

Table 1. Mood’s median test: birth weight versus COVID-19.

Fig. 1. Boxplot of gestational age of neonates.

Table 2. Mood’s median test: gestational age versus COVID-19.

Two neonates were reported to be COVID-19-positive on nasopharyngeal swab obtained immediately after birth, but the mode of infection remains unclear; 16.3% (53) of pregnant women were mildly symptomatic COVID-19-positive (most common symptoms noted were fever, cough, abdominal pain, anorexia, chest tightness, diarrhea, dyspnea, expectoration, fatigue, and headache), while 81.23% (264) of them were asymptomatic; and 2.46% (8) mothers had severe COVID-19 infection and required an extended duration of hospital stay (7 or more days) (Alimohamadi et al., 2022).

Ten neonates born to COVID-19-positive mothers required resuscitation (p=0.03), with seven of them presenting 1- and 5-minute APGAR scores of less than 6/10. Neonates born to COVID-19-positive mothers had a significantly higher need for resuscitation than those born to COVID-19-negative mothers (Table 3).

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Discussion

Pregnant women may be more susceptible to severe respiratory virus infections because of physiological changes in their immune and cardiopulmonary systems during pregnancy. It is crucial to study the potential adverse effects of COVID-19 in pregnancy (Wang et al., 2021). Approximately 13.84% (45) of COVID-19-positive mothers delivered their babies preterm, i.e., before reaching 37 weeks of gestational age. The data were aligned with the 12.6% preterm rate in India (Pusdekar et al., 2020).

Table 3. Comparison of baseline characteristics and pregnancy outcomes in mothers with and without COVID-19.

Fig. 2. Boxplot of birthweight of neonates.

Fig. 3. Probability plot of birthweight of neonates.

Low birth weight is a predictive indicator of neonatal health. It increases the long-term risk of complications (Badran et al., 2021). Two-thirds of the fetal weight gain occurs beyond the 24th week of pregnancy, and since weight gain continues into the third trimester, there is a possibility that viral infections could impact this crucial phase of development (Konar, 2015). Neonates with low birth weight have a >20 times greater risk of mortality than neonates with birth weight of >2.5 kg (World Health Organization, 2023). Recent studies show that the prevalence of low birth weight in India is 18% (Singh et al., 2023). The average birth weight of babies born to COVID-19 infected mothers was 2.78 ± 0.53 kg compared to 2.81 ± 0.4 kg in noninfected mothers, with no significant deviations. The birth weights in both groups were similar to the average birth weight in India, i.e., 2.8–3 kg (Krishnan et al., 2014).

Seven stillbirth cases were observed due to various factors, such as low birth weight, preterm delivery, severe anemia (Hb <7 g/dl), and fetal distress in COVID-19-positive mothers. According to recent estimates, the stillbirth rate in India is approximately 13.9 per 1,000 births (Dandona et al., 2023). No maternal mortality was noted.

Daclin et al. (2022) stated that the rate of maternal complications was not increased in the cohort of patients infected with the virus. Neonatal outcomes [neonatal respiratory distress (5.9%, n=5/86, vs. 3.5%, n=3/86 and p=0.72), neonatal infection (0%, vs. 1.2%, n=1/86 and p=1), malformation (none in both groups), or transfer in NICU (5.9%, n=5/86, vs. 5.8%, n=5/86 and p=1)] were not significantly different between the two groups (Daclin et al., 2022). Studies from Hail, Saudi Arabia, concluded that COVID-19 during pregnancy does not increase the risk of preterm birth or LBW of the babies, which is consistent with our findings (Parveen et al., 2022).

Studies by Beusekom (2020) stated that the pooled prevalence of preterm delivery in COVID-19 infected pregnant women was 23%, which is higher than the 5% rate in the European general obstetric population. A systematic review by the American Physiological Society included 3,110 COVID-19-positive women and reported a 30% preterm birth rate along with fetal growth restriction (Wastnedge et al., 2021). A study by Simbara et al. (2023) found that COVID-19 infection during pregnancy may increase the risk of adverse pregnancy outcomes, such as preterm delivery, maternal mortality, NICU admission, and neonatal death, in the group with COVID-19 infection [14.32 (95% CI: 12.07 and 16.91), 0.65 (95% CI: 90.37 and 1.130), 14.57 (95% CI: 10.15 and 20.48), and 0.65 (95% CI: 0.51 and 0.83)]. The study also found that pregnancy loss and SARS-CoV-2-positive neonates in the lower middle income group are higher than in high income (Simbar et al., 2023). A retrospective study by Alasarrje et al. (2022) found that infection with COVID-19 had a significant effect on pregnancy outcomes and that infected women were more likely to have higher incidence rates of adverse perinatal outcomes in both mothers and newborns. Our study presents contrasting findings regarding the increased prevalence of preterm delivery and LBW among COVID-19 infected mothers, possibly influenced by factors such as the shorter duration or milder severity of the infection during the 3rd trimester of pregnancy.

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Limitations

Due to the limited sample size from a single hospital in Bengaluru, the study did not represent the broader population. Further study with a larger sample size could provide additional insights.

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Conclusion

Although COVID-19 infection during pregnancy has been a concern, this study did not find a significant impact on key birth outcomes, such as gestational age at delivery and birth weight, in the study population. However, given the evolving nature of the COVID-19 pandemic and the potential for long-term effects, continued monitoring and research are essential to fully understand the implications of COVID-19 on maternal and fetal health.

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Acknowledgments

Gratitude is extended to the obstetricians for their exceptional service in delivering babies during the COVID-19 pandemic and for helping us collect data for the study. Their dedication and professionalism to adversity are commendable.

Conflicts of interest

The authors declare no conflicts of interest.

Funding

This research was supported by the Rajiv Gandhi University of Health Sciences.

Ethical statement

The Institutional Ethics Committee approval was obtained in August 2023 (IEC approval no.: SABVMCRI/IEC/RP/143/22-23).

Data availability

The data are not publicly available as they are confidential and no one other than the principal/coinvestigators will be allowed to access the data.

Author’s contribution

Conceived and designed the analysis: Naladala Disha Chowdary

Collected the data: Naladala Disha Chowdary, Arjun Santosh Menon, and Shravanthi V

Contributed data or analysis tools: Srinivas Naidu and Usha Kantharajanna.

Performed the analysis: Naladala Disha Chowdary and Chaitra M.S.

Wrote the paper: Naladala Disha Chowdary and Chaitra M.S.

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