How safe is COVID-19 vaccination among pregnant women and its outcome -A hospital-based retrospective study in Indian population

Following the emergence of COVID-19 in late 2019 and the subsequent pandemic, India authorized emergency use of Covishield (chimpanzee adenoviral vector vaccine) and Covaxin (inactivated whole virion vaccine) in 2021. During India’s second wave, increased maternal infections and some deaths heightened concern for pregnant women, a group initially excluded from vaccine trials. Based on accumulating evidence and global experience, India’s NTAGI recommended COVID-19 vaccination for pregnant women on July 2, 2021. However, safety concerns persisted about potential adverse pregnancy outcomes and vaccine-related AEFI in pregnancy. This study aimed to evaluate the safety of COVID-19 vaccination during pregnancy by assessing AEFI and key pregnancy and neonatal outcomes in an Indian hospital cohort.

The discussion references multiple studies indicating no increased risk of adverse pregnancy outcomes with COVID-19 vaccination. International data (Chicago, Taiwan, Mayo Clinic, London) on mRNA vaccines suggest no elevated risks for congenital anomalies, stillbirth, miscarriage, preterm delivery, or postpartum complications. Systematic reviews and meta-analyses (Prasad et al., Carbone et al., Shafiee et al.) corroborate vaccine safety in pregnancy and potential effectiveness. Additional evidence suggests high vaccine effectiveness and passive immunity to newborns via placental transfer and breast milk antibodies (Collier et al.). The present study adds data from India on Covishield and Covaxin, vaccine platforms less represented in earlier literature.

Design: Hospital-based retrospective cohort study as part of the Healthy Mother Healthy Child (HMHC) project at Sumandeep Vidyapeeth. Setting: Dhiraj Hospital, Vadodara, Gujarat, India, serving Vadodara and surrounding villages. Period: Deliveries from July 2021 to April 2022. Population: All women delivering at Dhiraj Hospital during the study period (n=2064); after exclusions (incomplete ANC care, not delivering at the hospital, lost to follow-up, or lack of initial consent), n=1974 were included. Data sources: HMHC project records and software capturing socio-demographics, ANC care, lab investigations, USG, expert advice, vaccination status (type and timing), hospitalization and delivery details, and neonatal outcomes. Exposure groups: Vaccinated (received at least one dose of Covishield or Covaxin during pregnancy) vs unvaccinated. Timing of vaccination by trimester was recorded. Outcomes: AEFI (self-reported), gestational age at birth (preterm <37 weeks, term 37–42 weeks, post-term >42 weeks), low birth weight (LBW), congenital anomalies, NICU admission, intrauterine death (IUD). Statistical analysis: Conducted using Epi Info and Microsoft Excel. Incidence rates and relative risk (RR) with 95% confidence intervals (CI) were calculated to compare outcomes between vaccinated and unvaccinated groups; p-values reported for significance testing. Ethics: Approved by the institutional ethics committee; informed consent obtained at initial recruitment.

- Cohort: 1974 women; 531 (27%) vaccinated during pregnancy (Covishield 511, 96%; Covaxin 20, 4%); 1443 (73%) unvaccinated. - Timing of vaccination: 29% first trimester, 51% second trimester, 20% third trimester among vaccinated. - AEFI (n=531 vaccinated): 46% reported any AEFI; most common were fever 28% (147/531) and injection site pain 11% (55/531); body ache 3% (16/531); headache 2% (13/531); weakness 2% (13/531); 54% reported no side effects; no serious AEFI (no hospitalizations or deaths). - COVID-19 infection history: Among those with data, 13 vaccinated and 3 unvaccinated mothers reported prior/during-pregnancy COVID-19 infection; the vast majority in both groups had no infection history. - Gestational age at delivery (vaccinated vs unvaccinated): Preterm <37 weeks 8% (42/531) vs 13% (183/1443); term 88% (468/531) vs 87% (1258/1443); post-term 4% (21/531) vs ~0% (2/1443). - Low birth weight: Overall LBW 776/1974. Incidence 40% in vaccinated vs 39% in unvaccinated; RR 1.0215 (95% CI 0.903–1.154), p=0.73 (not significant). - Congenital anomalies: 18 total; 3 (0.6%) in vaccinated vs 15 (1%) in unvaccinated; RR 0.543 (95% CI 0.158–1.869), p=0.3335 (not significant). - NICU admissions: 210 total; 8% in vaccinated vs 12% in unvaccinated; RR 0.6997 (95% CI 0.508–0.964), p=0.028 (significant, lower in vaccinated). - Prematurity: RR 0.6237 (95% CI 0.453–0.859), p=0.0039 (significant, lower in vaccinated). Overall, vaccination was not associated with increased LBW or congenital anomalies, and was associated with reduced prematurity and NICU admissions.

The study addressed the central safety question of COVID-19 vaccination during pregnancy. AEFI among pregnant women were predominantly mild (fever, injection site pain) with no serious events, and were reported at lower frequency than in some general population studies. Crucially, vaccination was not linked to higher risks of low birth weight or congenital anomalies. On the contrary, vaccinated mothers had significantly lower risks of preterm birth and NICU admissions, suggesting a protective effect, potentially via reduced maternal morbidity or systemic inflammation associated with COVID-19. These findings align with international literature on mRNA vaccines showing no increased adverse pregnancy outcomes and potential benefits, and extend evidence to Indian vaccine platforms (Covishield and Covaxin). The demographic profile indicates substantial rural uptake, suggesting effective public health messaging and accessibility in the study region. The results support recommendations to vaccinate during any trimester and provide reassurance for family and primary care physicians counseling pregnant patients.

This first Indian hospital-based cohort evaluating Covishield and Covaxin in pregnancy found both vaccines to be safe with no increase in adverse pregnancy outcomes. AEFI were generally mild and less frequent than reported in many general population cohorts. Vaccination was associated with reduced prematurity and NICU admissions. These findings support continued recommendation of COVID-19 vaccination for pregnant women in any trimester and can bolster confidence among clinicians and families. Future studies could include multicenter, community-based cohorts and larger samples for vaccine-specific analyses, especially for Covaxin.

Single-center hospital-based retrospective design limits generalizability; community-based data were not included. The number of Covaxin recipients was small, necessitating combined analysis with Covishield for some outcomes, reducing power for vaccine-specific comparisons. Potential residual confounding cannot be fully excluded due to observational design and reliance on routine records and self-reported AEFI.