Discussion
Prematurity poses significant medical, emotional, physical, psychological and financial burden for affected infants, their support network, health systems, economies and society as a whole.25 VLBW and ELBW infants may be affected by significant neonatal morbidity, leading to long-term health concerns during childhood.26 A myriad of aetiological and antecedent factors could trigger VLBW and ELBW births and the effectiveness of preventive measures depends on precise understanding of causation.10 A pan-European study found rising VLBW and ELBW rates in most countries.27 Increase in multiple births as well as assisted reproduction techniques (ART) also contributed to the overall increase.27 Even though earlier literature suggests PPROM as a multifactorial biological process, accounting for 30%–40% premature births, more recent medical interventions (indicated PTB) account for a significant proportion of VLBW infants.27–29 Understanding cross-country differences also could inform strategies aimed at reducing prematurity.17 27
Pregnancy is an ideal opportunity to encourage positive behavioural changes.30 Pregnancy Risk Assessment Monitoring System in Ireland, National Institute for Health and Care Excellence guidelines as well as the ‘Safer Maternity Care’ document in UK are worthy initiatives targeting reduced VLBW and ELBW births.30–32 Prenatal period and foetal growth could be regarded as a matrix for our lives and societies.33 Heterogeneous origins of VLBW and ELBW rates could be influenced by environmental changes, modifiable population factors, nutritional variations, stress factors and socioeconomic status.17 However, the yet under-recognised, behavioural, sociocultural and socioenvironmental modifications and opportunities designed to prolong the intrauterine nurturing milieu could offer far more in improving birth rates of such high-risk infants.
Birthweight-based data capture and analysis
Even though there has been increasing acceptance of GA-based cohorting,7 29 more recent neonatal network and register-based studies comparing VLBW and VLGA cohorts found no difference in the prediction power for adverse outcomes between the two groups despite the inherent SGA bias within the VLBW group.20 Two models also showed equal power to predict mortality and utility for benchmarking.20
The VON database and NPEC recorded 612 Irish infants in 2017 with gestation less than 29+6/7 weeks.21 23 Among this national cohort only 16 (2.6%) had a birth weight above 1500 g, indicative of VLBW being an acceptable proxy for significant prematurity.21–23 Contribution of SGA to the national VON submission in 2017 for VLBW was 19.5% and assuming a representative regional sample, our cohort of VLBW would have 80.5% premature infants who are appropriate for GA.21 23 These proportions could be significantly different in developing countries with relatively high SGA contribution among the VLBW infants.
Mortality trends: ‘shift-to-left’ and ‘shift-to-right’
Coinciding with the twenty year trend in VLBW and ELBW live births, we have also analysed the stillbirth rate (‘shift-to-right’) and compared with that of the lockdown period. Even though WHO defines stillbirth for fetal demise >28 weeks and Centers for Disease Control and Prevention defines >20 weeks; Irish CSO and Health Service Executive applies >24 weeks and that definition was applied to the study population.22 34 In order to establish that the decline in VLBW and ELBW rate during the lockdown was not secondary to an unexpected increase in early pregnancy loss (EPL <12+6/7 completed weeks of gestation) or terminations or miscarriages/late fetal loss (<24 weeks of gestation) (collectively ‘shift-to-left’), additional EPAU statistics and labour ward level data were collected for 2016–2020 for the months of March to June. As UMHL admits all infants with birth weight <2000 g to the neonatal unit, we also ascertained the trend of low birth weight (LBW <2.5 kg) infants of 1500–2000 g category for 2016–2019 and compared that with lockdown in 2020.
There was no increasing trend for EPL, miscarriages or stillbirths at UMHL or the region during the study period, confirming no ‘displacement of vital statistics’ due to ‘shift-to-left’ or ‘shift-to-right’ in mortality as the main explanation for the VLBW and ELBW reduction (table 3).
Potential influence of termination of pregnancy on VLBW and ELBW rates
As one of the few developed regions of the world with abortion legally banned till late 2018, Ireland offers a unique opportunity to evaluate the natural history of VLBW and ELBW births and the wider relation to socioenvironmental alterations.35 Could the ELBW and VLBW figures in early 2020 be explained partially by the change in termination of pregnancy (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 9.2% and the national means for 2014–2017 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 involved MCA when no TOP was available. The TOPs undertaken in 2019 and 2020 from January to April (two in 2019 and four in 2020) beyond 12 weeks of gestation in our region were for MCA, in accordance with the national guidelines on compassionate grounds.35
COVID-19 lockdown triggered socioenvironmental and behavioural modifiers
The ‘Nature’s experiment’ through the COVID-19 lockdown could have triggered unparalleled and widespread socioenvironmental alterations to which pregnant women would have responded with appropriate behavioural and lifestyle modifications. Our observational study is not designed to suggest causality or even association of specific factors or their particular influence exerted on the unprecedented reduction of VLBW rate from 8.18 (95% CI 7.21 to 9.29) to 2.17 (95% CI 0.70 to 6.74) per 1000 live births for the January to April period. Potential modifiers, both facilitators and barriers, in socioenvironmental settings that would have influenced the mother–fetus pair to reduce the rates of VLBW or ELBW births during the COVID-19 lockdown and prelockdown weeks of enhanced public health vigilance are summarised as a pictorogram (figure 3). Each one of the postulated reasons is supported by previous studies, often controlling or observing one or two variables. However, the COVID-19 lockdown possibly offered an unprecedented summative contribution of the socioenvironmental changes and behavioural modifications to impart a contemporaneous beneficial effect during pregnancy. An account of the previous studies favouring socioenvironmental and behavioural influence on VLBW and ELBW births is offered as an online supplemental file.
Figure 3COVID-19 lockdown in Ireland and reduction of birth of VLBW and ELBW infants: potential contributors. VLBW, very low birth weight; ELBW, extremely low birth weight.
COVID-19 lockdown triggered unfavourable social issues and access to care
It could be argued that that the lockdown impacted negatively on a subset of pregnant population due to imposed restrictions and constraints on timely access to hospital-based monitoring for fetomaternal well-being, possibly resulting in delayed or deferred interventions. It is plausible that such deferred choices could have contributed to the observed reduction in VLBW and ELBW rates. Pregnant women may have chosen to avoid hospital visits to mitigate potential for COVID-19 transmission. COVID-19 triggered changes in obstetric service provision, staff shortage, reduced number of ultrasound scans and screening, all may have impacted clinical interventions.36 However, the absence of concurrent or paired increase in EPL or miscarriages or stillbirths in our region, where the access to maternity emergency services were functioning uninterrupted throughout the lockdown, supports non-medical and societal contributions to observed significant reduction in the VLBW and ELBW numbers.
Learning from the lockdown and societal approaches to influence VLBW rates
Only three VLBW and no ELBW infant admissions to the only neonatal intensive care unit of one of the health regions of Ireland from 1 January to 30 April 2020, resulted in a reduction to zero of morbidity metrics primarily linked to extreme prematurity such as necrotising enterocolitis, retinopathy of prematurity and severe forms (grades 3 and 4) of intraventricular haemorrhage. While the generalisation of the morbidity reduction is limited by the small regional sample, our findings highlights the prevention of ELBW births, if not absolutely medically indicated, as an effective approach in improving the high-risk and high-cost complications associated with extreme prematurity.
Broadened preventive approaches based on socio-environmental alterations, stress reduction, nutritional optimisation and lifestyle modifications based on underlying individual genetic and epigenetic variations may be worth considering.25 These observations, if replicated in other regions globally during the pandemic and linked with varying levels of socio-environmental restrictions triggered by COVID-19, could offer novel perspectives and promising insights facilitating analysis of yet under-appreciated phenotypes of VLBW and ELBW births. Statistical modelling approaches and big-data analysis principles would also be critical.16
Our observed trend in VLBW and ELBW births, if an outcome of the COVID-19 enforced socioenvironmental and behavioural changes, suggest it is reasonable to postulate that, (1) the low numbers from early March onwards was influenced by the effects of the prelockdown period of extra public health vigilance that commenced in mid-February, (2) effects are immediate and (3) the effects of lockdown will be seen in coming months and sustainable until such time as normality influencers are operating again. However, postlockdown deterioration in socio-environmental factors or a ‘baby boom’ in late 2020 could increase the VLBW and ELBW rates.
With limited international data published to date, emerging report from Denmark suggested a nationwide reduction of extremely premature births in the order of 90% during COVID-19 lockdown, compared with the preceding 5 years.37 A quasi-experimental study from Netherlands is suggesting reduction in PTB of all strata during the various time windows of the lockdown, compared with the preceding ten years.38 Newspapers, television and radio broadcasters as well as social media outlets from around the world during the last 2 months also report the possibility of an unexpected variation in the very preterm and VLBW/ELBW rates from diverse regions where a COVID-19 lockdown was imposed.39–41 However, reports of status quo or even an increase in VLBW rates from certain cities and increase in stillbirth rate36 also raise the possibility that it is perhaps how pregnant women respond to the cumulative socioenvironmental alterations and what level of medical, social, familial and economic support systems are offered in different countries or regions during the lockdown that influences the fetomaternal outcome.
Limitations, interpretations and generalisability
The following limitations are acknowledged: (1) Inherent reservations posed by retrospective nature of the birth cohort data spanning over two decades from one health region of Ireland; (2) Even though the vast majority of the VLBW infants would be premature, concurrent contribution by SGA and rarely severe IUGR at term could be included. However, such an inclusion consistently over two decades should reduce the bias and the weight-based inclusion criteria would allow comparison to national data by CSO, NPEC and internationally through VON; (3) Inclusion of January 2020, when there was no lockdown or enhanced prelockdown public health measures. This was required to make comparison with the two decades of trends including the ‘first four calendar 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. However, we have extended our observation through the entire lockdown and the phase 1 and phase 2 of the easing as well (till end of June 2020) and confirmed that our initial observation sustained; (5) ELBW cohort could only be analysed with limitations considering the small number of births; (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, thus arguably postponing the GA of intervention. Thus, it could be viewed that the potential for reduced monitoring opportunities or the deferred early foetomaternal interventions during the lockdown could have also ‘shifted the band’ from ELBW and VLBW to LBW or normal weight and gestational category of infants; (8) Our observations could either be due to the cumulative socio-environmental alterations and maternal behavioural modifications or due to deferred early obstetric interventions or suboptimal timely access to the recommended antenatal monitoring. Our study is not designed to confirm causality or reaffirm associations and the postulated factors summarised in figure 3 and online supplemental file reflects compilation of already existing evidence; (9) Dataset from a regional sample in Ireland is relatively small and thus not strictly reflecting every society’s behavioural and socioenvironmental response to the country-specific components of COVID-19 lockdown and the offered support systems.
