The most common non-chromosomal congenital anomalies were neural tube defects (e.g., spina bifida and other developmental brain disorders), cleft lip and palate and congenital heart defects.
Researchers from Semmelweis University, Budapest, Hungary, studied more than 10,000 eligible articles. The conclusions were based on a comparison of data from 14 scientific papers published between 1964 and November 2022. The results have been published in the journal Viruses.
Dr. Ákos Mátrai, Assistant Lecturer at the Department of Obstetrics and Gynaecology of Semmelweis University, said:
“Pregnancy complications caused by viral infections have been the focus of attention in recent years due to Covid-19, and there are growing concerns that we might face similar pandemics in the future. In our study, we analysed how first-trimester influenza could affect newborns. The first three months are crucial as most of their organs develop.”
A total of 85,855 births were analysed for women aged 20-45.
The results show that the risk of birth defects can increase by 50% (1.5 times) on average if a mother-to-be catches the flu in the first trimester – compared to a healthy pregnancy.
In a more detailed comparison, the risk of neural tube defects can increase by an average of 148% (2.48 times). The significance of neural tube defects is outstanding, as they are amongst the most common causes of genetic abortions.
On average, the risk of developing cleft lip and palate can increase by a similar amount, also 2.48 times. These children often struggle with feeding difficulties and may develop hearing loss and speech problems.
The third large group is congenital heart defects which can increase by an average of 63% (1.63 times). Within this, the chance of developing aortic coarctation (narrowing of the aorta) can increase up to four times due to first-trimester maternal influenza infection.
Some analysed studies also reported a higher risk of limb development and eye anomalies.
Prof. Nándor Ács, Director of the Department of Obstetrics and Gynaecology at Semmelweis University, added:
The importance of prevention cannot be emphasised enough. Our results show that first-trimester flu can have serious implications as it is the most critical period in the development of the foetus. Therefore, we strongly recommend that every mum-to-be get the flu vaccine, even in the planning stages of pregnancy.
Previous studies have shown that it’s not the virus but the fever that causes complications. Therefore, it’s crucial to reduce the temperature in pregnant women if they fall ill. It is also well-known that taking folic acid and vitamins can help prevent congenital anomalies.
According to some estimates, congenital anomalies occur in 3-5% of pregnancies and are responsible for 20-25% of newborn deaths.*
According to the US-based Centers for Disease Control and Prevention, 39 to 51 million people contract influenza A, B, or C worldwide each year, mainly between December and March. The incubation period for the virus is about 48 hours, and recovery usually takes 3-7 days. Patients can then develop a secondary bacterial infection. In pregnant women, this can also lead to complications.
The Semmelweis research group is working on another large-scale study analysing the Hungarian Case-Control Surveillance of Congenital Abnormalities. The database contains information on almost 90,000 births in Hungary between 1980 and 2009. The scientists are trying to establish to what extent first-trimester flu can cause congenital disabilities. Their results have so far supported the conclusions drawn from the current international meta-analysis.
The role of influenza viruses is debated in the origin of congenital abnormalities. Some epidemiologic studies have shown a slight increase in birth defects, while others did not find any after influenza epidemics. It is not clear whether there is a direct link between flu infection and congenital disabilities or whether it exerts an indirect teratogenic effect. High fever associated with influenza was assumed to play a causative role in this pathologic process.
*Etiology and clinical presentation of birth defects: population based study. AUFeldkamp ML. 2017;357:j2249. Epub 2017 May 30.
Photo: Attila Kovács, Bálint Barta – Semmelweis University; Cover photo (illustration): Envato Elements
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