key: cord-1020075-97exroiv authors: Philip, R. K.; Purtill, H.; Reidy, E.; Daly, M.; Imcha, M.; McGrath, D.; O'Connell, N. H.; Dunne, C. P. title: Reduction in preterm births during the COVID-19 lockdown in Ireland: a natural experiment allowing analysis of data from the prior two decades. date: 2020-06-05 journal: nan DOI: 10.1101/2020.06.03.20121442 sha: 5eae06c6c0d9d6b771e452ba898a0e2d91c83e06 doc_id: 1020075 cord_uid: 97exroiv 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. Over 15 million babies are born too early, too sick and too small in the world every year. One million of these infants die. 1 Preterm birth (PTB), below 37 weeks of gestation, contributes significantly to infant mortality. 2, 3, 4, 5 In 2016, 46% of the underfive mortality globally was contributed to by neonatal deaths within the first 28 days of life and the main contributor was prematurity. 5 PTB rate is increasing in most developed and developing countries and a significant proportion of spontaneous PTB is of unknown aetiology. 2, 6 The frequency of PTB varies from 5-9% in Europe, 10 .6% in North America to 11.9% in Africa. 7, 8 While repeated PTB is reported, most All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint preterm very low birth weight (VLBW, <1,500 gm) and extremely low birth weight (ELBW, <1,000 gm) infants are born to women with no prior history of PTB. 5, 9 Prevention of PTB is considered a public health priority. Despite the obvious and growing relevance, progress has been modest. 10 Currently there is no standardised and effective strategy to prevent PTB, and implementation of socio-cultural approaches to mitigate the risk of PTB would require better elucidation of nonmedical factors that are both under-recognised and under-evaluated. 11 Although the causal biological mechanisms mediating PTB are poorly understood, preterm premature rupture of membranes (PPROM) complicates one third of all PTB. 12 Suggested alternate biological antecedents include amnionic inflammasome, alterations to vaginal microbiota, variations in cytokines, chemokines and other inflammatory modulators, as well as intra-amniotic inflammation (IAI) and infections. 13, 14, 15 It has been suggested that socio-environmental phenotype could offer insights and recognising the sources of heterogeneity and phenotypic plasticity in PTB may inform eventual effectiveness of preventive measures. 16, 17 Ireland offers a unique opportunity to evaluate PTB as it has been one of the very few developed countries that legally prohibited termination of pregnancy (TOP) or abortion until the 'Regulation of Termination of Pregnancy Act' was passed on 20 th December 2018 with services initiated on 1 st January 2019. 18 In that specific setting, there existed an opportunity to compare data from the pre-TOP era with 2020 data to determine the potential influence on PTB rates due to socio-environmental measures implemented as Ireland's prudent response to the SARS-CoV-2 virus (COVID- 19) pandemic. In effect, these measures constituted a national lockdown and may possibly have influenced the health and wellbeing of pregnant women and their All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint unborn infants. We wished to assess these redefined social and behavioural boundaries that could foster an environment encompassing elements that are favourable to pregnancies reaching full term. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. There were no overarching significant alterations to the antenatal, obstetric or intrapartum care pathways initiated for the pregnant women at UMHL or our health region from January-April of 2020 compared to preceding years. This offered us the opportunity to hypothesise whether the non-medical, community-based, socioenvironmental determinants and modifiable behavioural factors brought on by the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint Irish public health responses to COVID-19 pandemic and lockdown would be of significance to our observed temporal trends in PTB rates. Fully anonymised and de-identified dataset fulfilling general data protection regulation (GDPR) compliance was prepared for statistical analysis. 24 Significance of temporal trends in the VLBW and ELBW rates per 1000 births were assessed using Poisson regression, where time was entered as a continuous variable. Poisson regression with 95% Wald confidence intervals and rate ratio analysis were used to compare the observed VLBW rate for Jan-April of 2020 at UMHL to historical data. Estimates of the prevalence of VLBW and ELBW per 1000 births pre-2020 assessed the potential impact of January -April 2020 regional data on the national expectation of VLBW for 2020 in Ireland (based on the previous published Irish data from VON and CSO). 21, 22, 23 All data were analysed using IBM SPSS Statistics V.26. Patient and public involvement (PPI) was initiated at the outset of research planning. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint care programmes for 2020. INHA also nominated a parent of a premature VLBW infant to be an independent external reviewer of VLBW and ELBW data for 2020. Designated representative of the patient advocacy group is a member of the study team and authorship of the manuscript. Once published, the relevant findings of the study will be disseminated through the websites of INHA www.inha.ie and EFCNI www.efcni.org Guidance for Reporting Involvement of Patients and the Public (GRIPP2) reporting checklist as applicable to this study has been fulfilled. (Appendix 1) Considering the unprecedented and significant reduction of the VLBW and ELBW numbers observed during the lockdown and pre-lockdown phases of extra public health vigilance, we have verified the accuracy and authenticity of primary data capture with external independent professionals and patient representative (as part of the PPI initiative) who are not members of the research team or authorship. University Hospital Limerick Research Ethics Committee approval was granted for the study. Over the last twenty years UMHL had 93,018 live births and during the four months of January to April from 2001 to 2020 there were 30,705 live births. Annual live births, annual ELBW and VLBW rates as well as the respective numbers for 1 st January to 30 th April of each year for the last two decades are summarised in Table 1 . Poisson regression analyses of the 2001 -2019 data did not find any evidence of All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. The VLBW rate per 1000 live births from the aggregated regional numbers for 2001-2019 yearly data was computed to be 8.41 (95% Wald CI: 7.83, 9.04), providing a forecasted annual rate for 2020. A continuation of the 73% reduction from forecast in the January-April VLBW rate for the health region for the remainder of 2020 would forecast a rate of 2.27 VLBW per 1000 live births. However, a reversal to the regional population's pre-lockdown behavioural and socio-environmental status quo could increase the rate towards the historical rates. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint The forecast for the 2020 national VLBW rate is taken from the 2014-2017 VON date for Ireland, giving a mean of 9.37 per 1000 live births, no trend is evident. (Table 3 ) If the national VLBW rate reflects the observed regional rate of 2.17 (95% Wald CI: 0.70, 6.74) (January-April 2020), the upper confidence limit estimates the number of VLBW infants to be born in Ireland in 2020 could be reduced to approximately 400 per 60,000 births (historically 500-600). (Table 2 Prematurity poses significant medical, emotional, physical, psychological and financial burden for the affected infants, their support network, health systems, economies and society as a whole. 25 PTB through significant neonatal morbidity also leads to long-term health concerns during childhood. 26 A myriad of etiologic and antecedent factors could trigger PTB and the effectiveness of preventive measures depends on our precise understanding of the causation. 10 A pan-European study found rising PTB rates in most countries and an increase in multiple births as well as assisted reproduction techniques (ART) also contributed to the overall increase. Understanding cross-country differences also could inform strategies for PTB reduction. 27 Pregnancy is an ideal opportunity to encourage positive behavioural changes. 28 Pregnancy Risk Assessment Monitoring System (PRAMS) in Ireland, National Institute of Clinical Evidence (NICE) guidelines as well as the 'Safer Maternity Care' All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint document in UK are worthy initiatives aimed at PTB reduction. 28, 29, 30 However, the yet under-recognised, behavioural, socio-cultural and socio-environmental modifications and opportunities designed to prolong the intrauterine nurturing milieu could offer far more to reduce PTB rates. Prenatal period and foetal growth could be regarded as a matrix for our lives and societies. 31 As one of the very few developed regions of the world with abortion legally banned till late 2018, Ireland offers a unique opportunity to evaluate the natural history of PTB and the wider relation to socio-environmental alterations. Could the very low ELBW and VLBW figures in early 2020 be explained partially by the change in TOP law, allowing for TOP beyond 12 weeks gestation in the presence of major congenital anomalies (MCA) that limits foetal or neonatal viability? Examination of our regional and national historical data suggest not. Historical mean prevalence of MCA among our regional cohort of VLBW from 2000 to 2018 (two decades of no TOP) was a mean of 9.2 % and the national mean for 2014, 2015, 2016 and 2017 were 9%, 7%, 9% and 8% respectively (55/596, 42/622, 54/593 and 51/612). 23 That is, less than 1 in every 10 VLBW had the presence of MCA when no TOP was available. The TOPs undertaken in 2019 and 2020 from January-April (two in 2019 and four in 2020) beyond 12 weeks of gestation were for All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint MCA in our region, in accordance with the national guidelines on compassionate grounds. 18 There was no increasing trend for the stillbirth rate (SBR) of UMHL or the region during the study period, confirming no 'displacement of vital statistics' as an explanation for the VLBW reduction. The 'Nature's experiment' through the COVID-19 lockdown triggered unparalleled and widespread socio-environmental alterations which we hypothesise as the plausible explanation for PTB of VLBW rate to fall from 8.18 (95% CI: 7.21, 9.29) to 2.17 (95% CI: 0.70, 6.74) per 1000 live births for the January -April period. Specific modifiers, both facilitators and barriers, in the socio-cultural and socio-environmental settings that in our view would have influenced the mother-foetus pair to reduce the chances for PTB during the COVID-19 lockdown and pre-lockdown weeks of enhanced public health vigilance are summarised below ( Figure 3 ). Psychological stresses increase the likelihood of PTB. Positive benefits from familial support have been reported. 9 Male partner involvement on reducing PTB rates has been suggested. 34 Compared to women who reported no partner involvement and support during pregnancy, those who had it reported better psychological wellbeing. 35 There is strong evidence that pregnancy-specific anxiety, depression and stress increase the likelihood PTB. 36 Impacts of on-call work during pregnancy in relation to stress and sleep are not well established. 37 Measures of psychological distress including alterations in blood corticotrophin-releasing hormone (CRH) levels and cortisol are associated with PTB. 38 The biologic pathways underlying stressinduced PTB remain poorly understood. 39 We postulate therefore that the reduced All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint pregnancy associated stress and increased support systems available during the COVID-19 lockdown could be contributory factors in the low levels for PTB of VLBW seen in the region. Studies suggest an association of shift work, fixed night shifts and long working hours during pregnancy with PTB. 40, 41 Women working more than 55.5 hours (vs 40 hours) per week had a 10% increase in the odds of having a PTB. 40 Danish National birth cohort study associated shift work with an increase in small-for-gestational-age (SGA). 42 Physically demanding work while pregnant increases PTB as per systematic review and meta-analysis. 40, 43 A threefold increase in PTB was reported in women whose daily work entailed trunk bending for over one hour. 44 Bed rest in hospital or at home is widely recommended as a conventional practice to prevent PTB through the possible reduction of uterine activity. While sufficient rest and relaxation seems appropriate, Cochrane review concluded neither supporting nor refuting the use of prolonged bed rest at home or in hospital, to prevent PTB. 45 It is possible that the change in work practices due to the COVID-19 lockdown had the added benefit of reducing prematurity. A Unites States study exploring temporal patterns of PTB observed a periodicity for PTB rates. 46 Association between ambient air pollution (AAP) exposure during pregnancy and PTB has been reported. 26, 47, 48 Particulate matter, nitrogen dioxide, ozone, and carbon monoxide were the most commonly used markers of AAP. 47, 48 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint Sulphur dioxide (SO 2 ) was the largest contributor to increase PTB and other agents were particulate matter (PM) 2.5 micron , PM 10 micron and NO 2. 26 One study from Wuhan, China linked PTB to the atmospheric pollutant, vanadium. 49 The relationship between atmospheric temperature and seasonal fluctuations to PTB has been suggested. 50 European pattern is discerned with a spring peak and in Asia and US a seasonal variance of up to 5-10% has been reported. 50 No major meteorological events were reported in Ireland during the 2020 lockdown in comparison to the preceding two decades and the observed decline in our VLBW rate is well beyond the variations in the natural annual temporal trends reported to date. Cumulative contribution to AAP improvement by a reduction in all modes of transport, reduced consumption of diesel and petrol, reduced production and distribution of goods and closure of factories, all led to reduced environmental pollution in UK and Europe during the lockdown. 51 'Growing up in Ireland survey' calculated the index for LBW arising from PTB and intrauterine growth restriction (IUGR) and an association with parental education and environmental conditions was observed. 52 The UK Bradford study found that a new variable of interest, financial strain, was associated with a significant increase in PTB. 53 Direct and timely financial assistance offered by the Irish Government during the lockdown to businesses, self-employed and employees who were temporarily laid off, possibly avoided financial strain on the pregnant families. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint Observational data suggest the influence of maternal under nutrition in spontaneous PTB, which support a role for optimal maternal pre-pregnancy and in-pregnancy nutritional status in determining gestational length. 6 A low maternal body-mass index (BMI) was associated with spontaneous PTB. 7 Compared to no exercise during pregnancy, those taking appropriate leisurely exercise lowered the risk of PTB and placental weight gain could partially mediate the association between exercise during pregnancy and PTB. 54 Irish lockdown allowed for outdoor exercise within a two kilometre radius of home and Government initiatives promoted online wellbeing and exercise choices through the 'Healthy Ireland' platform. 55 Susceptibility to infectious diseases is often modified during pregnancy. Alterations in immunity to allow for the foetal allograft to implant and thrive combined with the anatomical and physiological modifications underlie these susceptibilities. 56 It has been shown that relationship satisfaction reduces infectious diseases in pregnancy. 57 Behavioural changes promoted during and prior to the lockdown, including social distancing, enhanced hand hygiene and use of face masks potentially reduced the chances of common viral infections during pregnancy. In addition, the closure of crèche, day-care centres, child minding facilities and play schools that normally 'bring home' common infections further reduced the potential for infective agent exposure. 58 Adoption of WFH policies by pregnant women and their partners may have further reduced exposure to the 'microbial world' of the adult population. Consequently, there may have been a reduction in the likelihood of Influenza, parvovirus B19 and congenital cytomegalovirus (CMV) that are more significant infections during pregnancy, with acknowledged associations with PTB. 58,59,60,61 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint Irish national lockdown has brought down overall vehicular traffic, reduced the commuting to and from work locations, avoided early start and late return to home, attenuated traffic-related stresses and improved atmospheric air pollution. Arguably, the potential for crashes involving pregnant women should be low as well. After a single crash, pregnant drivers had increased rates of PPROM and PTB. 62, 63 Evaluation of potential adverse foetal outcome using a 26 weeks pregnant woman manikin has previously demonstrated significant harm using common accident scenarios. 64 An observational study reported increased PTB following air travel, however large multi-centric studies would be warranted before drawing conclusions and the contribution to our study cohort would be low based on population characteristics. 65 During a lockdown or similar measures, depending on the socioeconomic factors and population characteristics, there is potential for upward or downward trends in domestic abuse or Intimate partner violence (IPV). The Irish Government launched proactive advertisement campaigns early in the lockdown period to educate and encourage measures against the potential for IPV. IPV is an important public health problem and an association between IPV and PTB has already been demonstrated. Prevalence of IPV was 14.9% in an Australian study and the main precipitating cause of PTB was antepartum haemorrhage. 66 Psychological abuse by partner was associated with increased risk PTB in one South Indian study. 67 9. Cigarette smoke, coffee, alcohol, prescription drugs and street drugs All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint Approximately 11% of Irish women smoke during pregnancy and 28% of those who smoke while pregnant had SGA infants compared to non-smokers at 13%. 68 Both active and passive (second-hand or environmental) tobacco smoking during pregnancy is associated with risk of SGA and PTB. 69, 70 PTB has been reported for women with drug dependence, cocaine and poly-substance being at the highest risk. 71 Studies evaluating alcohol consumption during pregnancy are often overshadowed by bias attributable to unmeasured confounders and varying or no impact on PTB rates has been reported. 72 Meta-analysis showed that high consumption of coffee during pregnancy is associated with low birth weight (LBW) and PTB. 73 On the other hand certain herbal preparations claim myorelaxant, anti-inflammatory and immunomodulatory properties and were reported as useful in preventing PTB associated with inflammation and infection. 11 While figures relating to cigarette smoking, alcohol consumption and coffee intake in pregnant women during the Irish lockdown are not yet available, it is hypothesized that with enhanced surveillance by enforcement agencies during this time, the availability, opportunities and the distribution for the illicit drug trade may have been reduced. Maternal immunization schedules are increasingly coming under the spotlight as part of the 'life-course' immunization programmes for the role that they play in improving maternal, foetal, and neonatal health. 74 Even though not primarily targeted to reduce PTB, influenza vaccination during pregnancy indirectly reduces PTB through the reduction of maternal morbidity. 74 Perhaps the lockdown afforded pregnant women All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint the opportunity to optimize preventive approaches including immunizations; however ease of access to services apparently was not uniform. Statistical modelling approaches and big-data analysis principles would also be critical in this journey to reduce PTB. 16 Standardized prenatal care and timely perinatal interventions could inherently lead to medically induced PTB, while rendering the desired reduction of foetal and maternal All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint morbidity and stillbirths. 76, 77 Medicalization of the physiological process of pregnancy is often criticized for excessive monitoring and interventions, most notably in health systems rooted on fee payment at point-of-care, private health insurance or reimbursements. 78 effects are immediate, and c) the effects of lockdown will be seen in coming months and sustainable until such time as normality influencers are operating again. However, post-lockdown deterioration in socio-environmental factors or a 'baby boom' in late 2020 could increase the PTB rates. The following limitations are acknowledged: 1. Inherent reservations posed by retrospective nature of the birth cohort data spanning over two decades; 2. Even though the vast majority of the VLBW infants would be premature, rarely severe intrauterine growth restriction (IUGR) at term could be included. However, such an inclusion consistently over two decades should reduce the bias and the weightbased inclusion criteria would allow comparison to national data by CSO, NPEC and internationally through VON; 3. Inclusion of January 2020, when there was no official lockdown or enhanced pre-lockdown public health measures. This was All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint required to make comparison with the two decades of trends including the first four months; 4. Completion of the study prior to the official finish of lockdown was to facilitate ease of comparison against the coded historical monthly data, timely data completion and analysis; 5. ELBW category could only be analysed with limitations considering the small number of births on a monthly basis; 6. We caution the 'no abortion policy' that Ireland followed till late 2018, when making international comparisons; 7. The lockdown could have deferred what should have been medically offered early during pregnancy as well, thus arguably postponing the gestational age of intervention. Thus it could be viewed that the potential for reduced monitoring opportunities or early foeto-maternal interventions during the lockdown could have 'shifted the band' from VLBW to LBW infants; 9. Our observations are suggestive of potential associations of the socio-environmental and behavioural modifiers with reduced PTB and the study is not designed to evaluate causality. Moreover, our dataset from a regional sample in Ireland is relatively small and thus not strictly reflecting every society's behavioural and socio-environmental response to the COVID-19 lockdown. The Irish national lockdown in response to SARS-CoV-2 virus (COVID-19) pandemic and the cumulative effects of socio-environmental variables such as maternal behavioural modifications, opportunities to work-from-home, potential reduction in work related stresses, possible alleviation of physical strain related to work and commuting, optimal opportunities for rest and sleep, likely increase in partner presence and support at home, reduced exposure to infections, improved opportunities for nutritional support and exercise as well as the positive alterations in All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint environment and air pollution, all would have possibly resulted in a reduction in PTB involving ELBW and VLBW infants. In the context of achieving sustainable development goals (SDG) and to reduce the under-five mortality globally, prematurity rate would be the most important 'curve to bend'. 80 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. The corresponding author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained. There are no individual study participants to disseminate the results to. Neonatal patients advocacy charity (INHA) involved in the study will be sent a copy of the article when published. The authors intend to disseminate the study findings through INHA website and other media so that the results will be available for the wider patient and public communities. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 5, 2020. . https://doi.org/10.1101/2020.06.03.20121442 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted doi: medRxiv preprint Time Period Births VLBW Rate (Wald 95% CI) Rate Ratio (95% CI) p-value