Maternal and Fetal Outcomes Following Influenza Vaccination in Pregnancy

This is a nationwide cohort study to assess maternal and fetal outcomes following vaccination with a quadrivalent influenza vaccine (QIV) during pregnancy.

Study Overview

• Status: Unknown
• Conditions: Pregnancy Related; Influenza Virus Vaccine Adverse Reaction
• Intervention / Treatment: Biological: influenza vaccine

Detailed Description

The Korean National Immunization Program (NIP) first introduced quadrivalent influenza immunization for all pregnant women in the 2020-2021 season. This nationwide cohort study is proposed to assess the risks of adverse maternal and fetal outcomes following vaccination with a quadrivalent influenza vaccine (QIV) during pregnancy. We will use the national health insurance database from the National Health Insurance Service (NHIS) linked with the national immunization program registry data from the Korea Centers for Diseases Control & Prevention (KCDC).

• Study Type: Observational
• Enrollment (Anticipated): 300000

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Pregnant women during the period of the national immunization program in South Korea.

Description

Inclusion Criteria:

• Pregnant women between September 22, 2020, and April 30, 2021.

Exclusion Criteria:

• Women aged <20 or >45 years
• Pregnancies with a chromosomal abnormality
• Pregnancies with exposure to a known teratogenic medication

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women vaccinated with a QIV; Women aged 20-44 years who had received a QIV during their pregnancy between September 22, 2020, and April 30, 2021, under the national immunization program in South Korea.	Biological: influenza vaccine; quadrivalent influenza vaccination in the flu seasons
Pregnant women unvaccinated with a QIV; Women aged 20-44 years who had not received a QIV during their pregnancy between September 22, 2020, and April 30, 2021, under the national immunization program in South Korea.	Biological: influenza vaccine; quadrivalent influenza vaccination in the flu seasons

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of adverse pregnancy outcomes	Spontaneous abortion, stillbirth, neonatal death, congenital anomaly, pre-term birth, fetal growth restriction, small for gestational age, and low birth weight, which are confirmed by diagnostic records in the NHIS database.	from delivery up to 1 year after birth
Risk of vaccine-related adverse events	Vaccine-related adverse events confirmed by diagnostic records in the NHIS database.	from delivery up to 1 year after birth
Risk of poor health outcomes in pregnant women	Hospital admission, emergency department visits, influenza infection, and hospitalization with influenza infection, which are confirmed by diagnosis and healthcare utilization records in the NHIS database.	from delivery up to 1 year after birth
Risk of poor health outcomes in neonates	Respiratory distress, neonatal intensive care unit admission, and hospital visits with neonatal infection or fever, which are confirmed by diagnosis and healthcare utilization records in the NHIS database.	from delivery up to 1 year after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of pregnancy-related complications	Pre-eclampsia/eclampsia, gestational diabetes mellitus, antenatal bleeding, postpartum hemorrhage, and maternal death, which are confirmed by diagnostic records in the NHIS database.	from delivery up to 1 year after birth

Collaborators and Investigators

• Sponsor: Sungkyunkwan University
• Collaborators: Government-wide R&D Fund project for infectious disease research (GFID)

Publications and helpful links

General Publications

• Baum U, Leino T, Gissler M, Kilpi T, Jokinen J. Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: A cohort study of pregnancies stratified by trimester of vaccination. Vaccine. 2015 Sep 11;33(38):4850-7. doi: 10.1016/j.vaccine.2015.07.061. Epub 2015 Aug 1.
• Macias Saint-Gerons D, Sola Arnau I, De Mucio B, Arevalo-Rodriguez I, Aleman A, Castro JL, Ropero Alvarez AM. Adverse events associated with the use of recommended vaccines during pregnancy: An overview of systematic reviews. Vaccine. 2021 Jul 30;39 Suppl 2:B12-B26. doi: 10.1016/j.vaccine.2020.07.048. Epub 2020 Sep 21.
• Walsh LK, Donelle J, Dodds L, Hawken S, Wilson K, Benchimol EI, Chakraborty P, Guttmann A, Kwong JC, MacDonald NE, Ortiz JR, Sprague AE, Top KA, Walker MC, Wen SW, Fell DB. Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study. BMJ. 2019 Jul 10;366:l4151. doi: 10.1136/bmj.l4151.
• Ludvigsson JF, Strom P, Lundholm C, Cnattingius S, Ekbom A, Ortqvist A, Feltelius N, Granath F, Stephansson O. Maternal vaccination against H1N1 influenza and offspring mortality: population based cohort study and sibling design. BMJ. 2015 Nov 16;351:h5585. doi: 10.1136/bmj.h5585.
• Hviid A, Svanstrom H, Molgaard-Nielsen D, Lambach P. Association Between Pandemic Influenza A(H1N1) Vaccination in Pregnancy and Early Childhood Morbidity in Offspring. JAMA Pediatr. 2017 Mar 1;171(3):239-248. doi: 10.1001/jamapediatrics.2016.4023.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): October 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: SKKU-2020-FP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No