A prospective, longitudinal, case-control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero

Rachel A Hill; Atul Malhotra; Vathana Sackett; Katrina Williams; Michael Fahey; Kirsten R Palmer; Rod W Hunt; Hayley Darke; Izaak Lim; Vesna Newman-Morris; Jeanie L Y Cheong; Clare Whitehead; Joanne Said; Paulo Bignardi; Evelin Muraguchi; Luiz Carlos C Fernandes Jr; Carlos Oliveira; Suresh Sundram

doi:10.1186/s12887-023-03858-w

A prospective, longitudinal, case-control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero

BMC Pediatr. 2023 Jan 30;23(1):48. doi: 10.1186/s12887-023-03858-w.

Authors

Rachel A Hill^{1

2}, Atul Malhotra³, Vathana Sackett³, Katrina Williams^{3

4

5}, Michael Fahey³, Kirsten R Palmer^{6

7}, Rod W Hunt^{3

8}, Hayley Darke⁹, Izaak Lim^{9

10}, Vesna Newman-Morris^{9

10}, Jeanie L Y Cheong^{5

8

11}, Clare Whitehead^{5

12}, Joanne Said^{5

13}, Paulo Bignardi¹⁴, Evelin Muraguchi¹⁴, Luiz Carlos C Fernandes Jr¹⁴, Carlos Oliveira¹⁴, Suresh Sundram^{9

15}

Affiliations

¹ Department of Psychiatry, School of Clinical Sciences at Monash Health, Monash Medical Centre, Monash University, Level 3, 27-31 Wright St, Clayton, VIC, 3168, Australia. Rachel.hill@monash.edu.
² Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia. Rachel.hill@monash.edu.
³ Department of Paediatrics, Monash University, Clayton, VIC, Australia.
⁴ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
⁵ Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia.
⁶ Monash Women's, Monash Health, Clayton, VIC, Australia.
⁷ Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
⁸ Clinical Sciences, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁹ Department of Psychiatry, School of Clinical Sciences at Monash Health, Monash Medical Centre, Monash University, Level 3, 27-31 Wright St, Clayton, VIC, 3168, Australia.
¹⁰ Monash Medical Centre, Early in Life Mental Health Service, Monash Health, Clayton, VIC, Australia.
¹¹ Department of Neonatal Services, Royal Women's Hospital, Parkville, VIC, Australia.
¹² Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, VIC, Australia.
¹³ Maternal Fetal Medicine, Joan Kirner Women's & Children's at Sunshine Hospital, Western Health, Sunshine, VIC, Australia.
¹⁴ School of Medicine, Pontifical Catholic University of Paraná, Londrina, Paraná, Brazil.
¹⁵ Mental Health Program, Monash Health, Melbourne, VIC, Australia.

Abstract

Background: The Coronavirus disease (COVID-19) pandemic has created unprecedented acute global health challenges. However, it also presents a set of unquantified and poorly understood risks in the medium to long term, specifically, risks to children whose mothers were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Infections during pregnancy can increase the risk of atypical neurodevelopment in the offspring, but the long-term neurodevelopmental impact of in utero COVID-19 exposure is unknown. Prospective, longitudinal studies are needed to evaluate children exposed in utero to SARS-CoV2 to define this risk.

Methods: We have designed a prospective, case-controlled study to investigate the long-term impacts of SARS-CoV2 exposure on children exposed in utero. Women infected with SARS-CoV-2 during pregnancy will be recruited from Monash Health, the Royal Women's Hospital and Western Health (Melbourne, Australia) and Londrina Municipal Maternity Hospital Lucilla Ballalai and PUCPR Medical Clinical (Londrina, Brazil). A control group in a 2:1 ratio (2 non-exposed: 1 exposed mother infant dyad) comprising women who gave birth in the same month of delivery, are of similar age but did not contract SARS-CoV-2 during their pregnancy will also be recruited. We aim to recruit 170 exposed and 340 non-exposed mother-infant dyads. Clinical and socio-demographic data will be collected directly from the mother and medical records. Biospecimens and clinical and epidemiological data will be collected from the mothers and offspring at multiple time points from birth through to 15 years of age using standardised sample collection, and neurological and behavioural measures.

Discussion: The mapped neurodevelopmental trajectories and comparisons between SARS-CoV-2 exposed and control children will indicate the potential for an increase in atypical neurodevelopment. This has significant implications for strategic planning in the mental health and paediatrics sectors and long-term monitoring of children globally.

Keywords: COVID-19; Neurodevelopment; Pregnancy; Prospective; SARS-CoV2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
COVID-19* / epidemiology
Case-Control Studies
Child
Female
Humans
Infant
Pregnancy
Pregnancy Complications, Infectious* / epidemiology
Prospective Studies
RNA, Viral
SARS-CoV-2

Substances

RNA, Viral