Irish and Danish studies: ‘Natural experiment’ of lockdown sees fall in rate of premature birth

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A drop in air pollution, reduced exposure to infections and lower levels of work-related stress have been suggested as the reasons for an “unprecedented” fall in the number of babies being born prematurely during lockdown, two separate studies have shown.

The Daily Telegraph reports that researchers in Ireland and Denmark took advantage of the “natural experiment” of lockdown to look at its impact on rates of pre-term birth.

The studies, neither of which have yet been published in peer-reviewed journals, both showed large falls in the numbers of babies born premature.

The report says the Irish study looked at the number of babies born weighing less than 3.3 pounds – a good proxy for pre-term birth – in the Limerick, Clare and North Tipperary region of the country between January and April this year. They found that the number of very low birth weight babies delivered during this period fell by nearly three quarters during lockdown compared to the average. For every 1,000 babies born during the period studied 2.17 were premature, researchers found.

The average rate for the region is nearly four times higher: 8.18 low birthweight babies are born for every 1,000 births.

Professor Roy Philip, consultant neonatologist and paediatrician at University Hospital Limerick and lead author of the study, was on holiday when lockdown began and on his return he noticed that there had been no orders for the breast-milk based fortifier used to feed the tiniest babies. Staff told him they had not ordered any because none of these babies had been born.

“There are normal fluctuations in the numbers of babies born but when they told me that none had been born for that length of time I thought that was unusual. And that triggered us to dive deeper into the data,” he said.

He was so surprised at the findings that he thought he had made a mistake. “I thought I wasn’t reading or calculating it correctly – I triple-checked the data to make sure it was correct,” he said.

The report says the team from Limerick only knew about the Danish study when it was published but Philip said the results were a “mirror image” of their own.

In the Danish study, researchers at Statens Serum Institut, Copenhagen, Copenhagen University Hospital Rigshospitalet, University of Copenhagen, and Stanford University School of Medicine, looked at the number of babies born in Denmark before 28 weeks gestation between 12 March, the day lockdown began, and 14 April this year and then compared this to the numbers born during the same period in the previous five years.
Some 58 very premature babies were born during the entire period but the rate was 90 per lower during lockdown, researchers found.

The pre-term birth rate was 0.19 for every 1,000 live births this year, compared to an average of 2.19 per 1,000 during the preceding years, the researchers found. The reasons for premature birth are still poorly understood and both the Irish and Danish researchers hope that “nature’s experiment” could provide vital information.

They point to a number of factors including a reduction in air pollution, less work-related stress and lower exposure to infections during pregnancy.

Philip is quoted in The Telegraph as saying it was hard to pinpoint the exact reason for the drop in premature birth rates in either study. “We have never had an opportunity in the recent past to control a population for all these social and environmental factors and behaviour aspects that lockdown brought. We think it’s a cumulative effect,” he said.

Philip said the findings may indicate that it would be better for women to take maternity leave earlier in the pregnancy, rather than just before the birth. However, he said more international data was needed. He added: “Our findings may not be exactly replicated in every region or country of the world. But what our study does point to is looking at the family-centred aspect of antenatal and pre-natal care.”

However, the report notes that Andrew Shennan, professor of obstetrics at King’s College London, said other factors could be at play. He pointed to data published in the Journal of the American Medical Association from St George’s Hospital in London that showed an increase in stillbirths during the pandemic, mainly associated with women not coming to hospitals for antenatal visits.
“Women are not being monitored. If I pick up a baby who is compromised I deliver them early – and that’s one of the causes of pre-term birth. Around a third of pre-term births take place because we decide to deliver them early,” he said.
“If there was a pollution effect or an environmental effect it might make a difference but to cause an 80 to 90 per cent reduction is to me completely implausible,” he said.

Abstract (Irish study)
Background: Aetiology of preterm birth (PTB) is heterogeneous and preventive strategies remain elusive. Socio-environmental measures implemented as Ireland s prudent response to the SARS-CoV-2 virus (COVID-19) pandemic represented, in effect, a national lockdown and have possibly influenced the health and wellbeing of pregnant women and unborn infants. Cumulative impact of such socio-environmental factors operating contemporaneously on PTB has never been assessed before.
Methods: Regional PTB trends of very low birth weight (VLBW) infants in one designated health area of Ireland over two decades were analysed. Poisson regression and rate ratio analyses with 95% CI were conducted. Observed regional data from January to April 2020 were compared to historical regional and national data and forecasted national figures for 2020.
Results: Poisson regression analysis found that the regional historical VLBW rate per 1000 live births for January to April, 2001 to 2019 was 8.18 (95% CI: 7.21, 9.29). During January to April 2020, an unusually low VLBW rate of just 2.17 per 1000 live births was observed. The rate ratio of 3.77 (95% CI: 1.21, 11.75), p = 0.022, estimates that for the last two decades there was, on average, 3.77 times the rate of VLBW, compared to the period January to April 2020 during which there is a 73% reduction. National Irish VLBW rate for 2020 is forecasted to be reduced to 400 per 60,000 births compared to historical 500 to 600 range.
Conclusion: An unprecedented reduction in PTB of VLBW infants was observed in one health region of Ireland during the COVID-19 lockdown. Potential determinants of this unique temporal trend reside in the summative socio-environmental impact of the COVID-19 dictated lockdown. Our findings, if mirrored in other regions that have adopted similar measures to combat the pandemic, demonstrate the potential to evaluate these implicated interdependent behavioural and socio-environmental modifiers to positively influence PTB rates globally.

Roy K Philip, Helen Purtill, Elizabeth Reidy, Mandy Daly, Imcha, Deirdre McGrath, Nuala H O’Connell, Colum P Dunne

Abstract (Danish study)
Objectives: To explore the impact of COVID-19 lockdown on premature birth rates in Denmark 21
Design: Nationwide register-based prevalence proportion study. 22 Participants 31,180 live singleton infants born in Denmark between March 12, and April 14, during 2015 to 2020 23
Main outcome measures: Main outcome measure was the odds ratio of premature birth, per preterm category, during 24 the lockdown period compared with the calendar match period in the five previous years. 25
Results: A total of 31 180 newborns were included in the study period, of these 58 were born extremely premature 26 (gestational age below 28 weeks). The distribution of gestational ages was significantly different (p = 0·004) during the 27 lockdown period compared to the previous five years. The extremely premature birth rate during the lockdown was 28 significantly lower than the corresponding mean rate for the same dates in the previous years (odds ratio 0·09 [95 % 29 CI 0·01 – 0·04], p < 0·001). No significant difference between the lockdown and previous years was found for other 30 gestational age categories. 31
Conclusions: The birth rate of extremely premature infants decreased significantly (~90 % reduction) during the Danish 32 nationwide lockdown from a stable rate in the preceding five years. The reasons for this decrease are unclear. 33 Identification of possible causal mechanisms might stimulate changes in clinical practice. Ideally, some cases of 34 extreme prematurity are preventable which may decrease infant morbidity and mortality.

Gitte Hedermann1, Paula L Hedley1, Marie Bækvad-Hansen, Henrik Hjalgrim, Klaus Rostgaard, Porntiva Poorisrisak, Morten Breindahl, Mads Melbye, David M Hougaard, Michael Christiansen, Ulrik LaustenThomsen


Full report in The Daily Telegraph
medRxiv (Irish study) abstract
medRxiv (Danish study) abstract
JAMA abstract

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