Background
The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women.
Objective
This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy.
Study Design
This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates.
Results
There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08–2.05; P =.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87–0.99; P =.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83–0.99; P =.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71–0.93; P =.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86–0.95; P <.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87–1.05; P =.32).
Conclusion
Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.
Introduction
The COVID-19 pandemic has disrupted the delivery of maternity care globally, with a recent systematic review concluding that maternal and fetal outcomes had significantly worsened during the COVID-19 pandemic. Some studies have reported increases in stillbirth and reductions in preterm birth (PTB), whereas others reported no changes. These differences are likely because of multiple factors, including differences in study methodology, resource setting, severity of lockdown restrictions, and COVID-19 caseload.
Why was this study conducted?
The COVID-19 pandemic has been associated with worsening of perinatal outcomes in many regions around the world. The Australian city of Melbourne is a unique case study for the association between pandemic restrictions and pregnancy outcomes because of the stringency and length of the lockdown, the lack of significant health system strain, and very low COVID-19 maternity caseload.
Key findings
Lockdown restrictions in Melbourne during 2020 were associated with a significant increase in preterm stillbirths and a significant reduction in iatrogenic preterm birth for fetal compromise.
What does this add to what is known?
Pandemic restrictions in a high-income setting with a negligible maternal COVID-19 case load may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. These findings should inform the maternity sector’s ongoing response to the COVID-19 pandemic.
The city of Melbourne, Australia, which has approximately 4000 births per month, experienced a prolonged period of lockdown restrictions commencing on March 23, 2020 through to March 14, 2021 ( Figure 1 ). The strictest period of lockdown in mid-2020 restricted leaving the house for reasons other than approved essential work, caring for dependents, obtaining medical care or essential food and services. Individuals were allowed 1 hour outside the home for exercise per day within a 5 km radius with a prohibition on all gatherings of >2 people and a curfew from 8 PM to 5 AM.
Numerous modifications to pregnancy care were concurrently adopted to mitigate the anticipated strain on health services and reduce infection risks. These measures included rapid transition to telehealth, hospital visitor restrictions, increasing the interval between in-person visits, reducing face-to face appointment time, changes to gestational diabetes screening, and ultrasound surveillance of fetal growth. Melbourne experienced relatively few maternal COVID-19 infections (<100 in 2020) and no associated maternal or perinatal deaths. This meant that metropolitan Melbourne experienced a unique set of circumstances not seen in other high-income countries: a prolonged period of significant social restrictions and major changes to antenatal care without an associated high burden of COVID-19 infections.
In mid-2020, all 12 Melbourne public maternity hospitals formed the Collaborative Maternity and Newborn Dashboard (CoMaND) for the COVID-19 pandemic project to internally monitor the effect of the pandemic on clinical quality indicators. Perinatal data collected for CoMaND were used here to analyse the impact of the lockdown on PTB, stillbirth, and utilization of maternity services.
Materials and Methods
Institutional review board approval
This study was given ethical approval from the Human Research Ethics Committees of Austin Health (reference number HREC/64722/Austin-2020) and Mercy Health (reference number 2020-031).
Study population
We extracted routinely-collected data on births ≥24 weeks from all 12 public maternity hospitals in Melbourne from January 1, 2018 to March 31, 2021. Approximately three- quarters of all hospital births in Melbourne occur in these study sites. Births in exclusively private hospitals and planned home births outside of publicly-funded homebirth programs were not captured. However, women planning a private hospital or home birth would typically be transferred to a public hospital if they were at risk of PTB <31 weeks or required tertiary maternal-fetal medicine care.
Exclusions
Infants with congenital anomalies, terminations of pregnancy (TOP), non-Victorian residents, and multiple pregnancies were excluded. We excluded births <24 weeks gestation, as TOP can be provided on maternal request up to this gestation, and management of PTB and preterm prelabor rupture of membranes < 24 weeks is variable and subject to parental discretion.
Definition of lockdown-exposed cohort and nonexposed controls
We defined the lockdown exposure period as March 23, 2020 to March 14, 2021, as this was a continuous period where the national stringency index (NSI) was ≥50 on the Oxford COVID-19 Government Response Tracker scale ( Figure 1 , B). The NSI threshold of 50 was used in accordance with the definition of lockdown in the International Perinatal Outcomes in the Pandemic study.
We used the calculated week of the last menstrual period rather than the week of birth to define the lockdown-exposed cohort to ensure that outcomes such as PTB would be measured using the denominator of births with a similar timing of lockdown exposure. We subtracted the infants’ gestational age at birth in completed weeks from the week of birth to obtain the week of calculated last menstrual period (cLMP). Using this cLMP, we defined a “lockdown-exposed” cohort comprising women for whom weeks 20 to 40 of gestation would have occurred during the lockdown period. This included women whose cLMP occurred during the 31 weeks from November 4, 2019 to June 1, 2020, both dates inclusive ( Figure 1 , B). To control for possible seasonality, the control group comprised women who had their cLMP during the corresponding calendar weeks commencing 1 and 2 years before the start of the exposed cohort (births with cLMPs in weeks commencing November 5, 2018 to June 3, 2019 and November 6, 2017 to June 4, 2018). These were assessed as a combined control group.
Outcome measures
We calculated all the outcomes using both the denominators of “all births” (live and stillbirths) and “live births,” with the exception of the stillbirth rate (calculated for “all births” only).
Primary outcomes
- 1.
Total stillbirth rate stratified by gestational age
- 2.
Total PTB (<37 weeks) rate
Secondary outcomes
- 1.
PTB <37 weeks: spontaneous and iatrogenic. An iatrogenic birth was defined as any birth without spontaneous onset of labor (either induced labor or no labor).
- 2.
PTB <32 weeks: total, iatrogenic, and spontaneous
- 3.
PTB <28 weeks: total, iatrogenic, and spontaneous
- 4.
Fetal growth restriction (FGR): total FGR, FGR at birth ≥37 weeks, <37 weeks, <32 weeks, and <28 weeks. FGR was defined as birthweight <third centile using local population sex-specific birthweight charts.
- 5.
Iatrogenic births for fetal compromise: ≥37 weeks, <37 weeks, <32 weeks, and <28 weeks. Indications for induction of labor and cesarean delivery were coded according to the Australian Institute of Health and Welfare Metadata Online Registry, which defines fetal compromise as “suspected or actual fetal compromise and intrauterine growth restriction.” Any documentation of suspected fetal growth restriction, antepartum abnormal cardiotocography, “fetal distress” (without labor), reduced fetal movements, oligohydramnios, abnormal umbilical artery Doppler studies, or placental insufficiency were included in this classification.
- 6.
Apgar score <7 at 5 minutes
- 7.
Special care nursery (SCN) admission
- 8.
Neonatal intensive care unit (NICU) admission
- 9.
First antenatal visit ≤12 weeks gestation: this refers to the first planned visit to a midwife or doctor during pregnancy, whether community- or hospital-based.
- 10.
Born before arrival (BBA): this refers to the rate of planned hospital births that occur before arrival, including unplanned births at home, in transit, or other locations.
Statistical analysis
No sample size calculation was performed, as this was a cohort defined by lockdown duration. Analyses of secondary outcomes were considered exploratory, and no adjustments for multiple comparisons were made. Perinatal outcomes were summarized as the proportion of all births (live births and stillbirths) and live births. Statistical significance was tested with the t-test or chi-squared test as appropriate. We performed multiple imputations by chained equation (MICE) to account for missing data from our dataset and created 5 imputed datasets (for statistical details see Supplemental file 1). We performed multivariable logistic regression analysis to obtain the adjusted odds ratio (OR) of the primary and secondary outcomes in the lockdown-exposed vs nonexposed cohorts. We adjusted for the following maternal covariates: maternal age, body mass index (BMI) at first antenatal visit, region of birth, need for interpreter (proxy indicator for primary language and categorized as yes or no), parity, socioeconomic status (assigned by maternal postcode), and smoking in pregnancy status. These covariates were chosen using subject matter knowledge. Statistical analyses were conducted using Stata 17 (release 17; StataCorp LLC, College Station, TX), and 2-sided P values below.05 were considered statistically significant. Because maternal BMI and smoking status were potentially on a causal pathway between lockdown restrictions and perinatal outcomes, we performed a sensitivity analysis without adjustment for these covariates.
We used Cox regression to derive the hazard ratios of stillbirths and PTB <37 weeks and Kaplan-Meier curves to plot the cumulative hazard of the outcomes of interest. We tested the proportionality of the hazards of control and exposed cohorts using Schoenfeld residuals. The ORs of the primary outcomes for each hospital were plotted in forest plots using meta-analysis of aggregated ORs per hospital. We used a fixed effect model to derive the pooled exponentiated effect measures (OR), because all the results are obtained on the same dataset, and the heterogeneity across all outcomes was small for all outcomes except overall PTB, with I 2 <30%.
Births included in run chart analysis
To examine the temporal patterns in outcomes during lockdown conditions, we also generated run charts by week of cLMP. Run charts are a commonly-used method for detecting nonrandom safety signals in healthcare where an outcome measure is charted over time with probability-based rules for safety signals such as shifts and trends. Only births with cLMP in the weeks from August 14, 2017 to June 22, 2020 were included in the run charts, comprising infants for whom weeks 20 to 43 of gestation occurred within the data collection period of January 1, 2018 to March 31, 2021. The prepandemic median rates for each outcome were calculated for the nonexposed cohort. A significant shift in a run chart was defined as 6 or more consecutive weeks all above or below the prepandemic median according to the established definitions.
Results
There were 147,367 births in the participating hospitals during the period from January 1, 2018 to March 31, 2021. After all exclusions, there were 118,705 births remaining for the run chart analysis by week of cLMP ( Figure 2 ).
Cohort analysis: lockdown-exposed vs nonexposed pregnancies
The lockdown-exposed cohort contained 24,817 births, and the control cohort contained a combined total of 50,017 births ( Figure 2 ). The characteristics of exposed and control groups are shown in Table 1 . The lockdown-exposed group differed significantly from the control group in terms of age, socioeconomic class distribution, maternal region of birth, and maternity service level, though the absolute differences were small. Details of the bivariate analysis are available in Supplemental Table 1 . The outcomes are presented using all birth denominators (live and stillbirths) in Table 2 and live birth denominators in Table 3 . The results all remained robust in the sensitivity analysis excluding covariates of smoking and BMI.
| Maternal characteristics | Exposed | Control | P value |
|---|---|---|---|
| (n=24,817) | (n=50,017) | ||
| Maternal age, mean (SD) | 31.9 (4.87) | 31.7 (4.95) | <.001 |
| Weight in kg, mean (SD) | 70.39 (17.13) | 70.20 (17.28) | .17 |
| Height in cm, mean (SD) | 163.17 (7.19) | 163.26 (7.05) | .14 |
| Smoking in pregnancy, n (%) | 1333 (5.37) | 2760 (5.52) | .41 |
| BMI categories, n (%) | |||
| <18 | 311 (1.29) | 654 (1.33) | .14 |
| 18–24 | 11,535 (47.96) | 24,167 (48.90) | |
| 25–29 | 7085 (29.46) | 14,106 (28.54) | |
| 30–34 | 2976 (12.37) | 6128 (12.40) | |
| 35–39 | 1318 (5.48) | 2647 (5.36) | |
| ≥40 | 824 (3.43) | 1718 (3.48) | |
| Region of birth, n (%) | |||
| Americas | 397 (1.61) | 744 (1.49) | <.001 |
| Australia and Associated Territories | 12,347 (50.05) | 24,433 (49.02) | |
| North Africa and Middle East | 1155 (4.68) | 2569 (5.15) | |
| Northeast Asia | 926 (3.75) | 2335 (4.68) | |
| Northwest Europe | 725 (2.94) | 1468 (2.95) | |
| Oceania including Antarctica | 955 (3.87) | 1913 (3.84) | |
| Southeast Asia | 2100 (8.51) | 4370 (8.77) | |
| Southern and Central Asia | 4823 (19.55) | 9408 (18.87) | |
| Southern and Eastern Europe | 484 (1.96) | 1064 (2.13) | |
| Sub-Saharan Africa | 755 (3.06) | 1543 (3.10) | |
| Parity, n (%) | |||
| 0 | 10,919 (44.00) | 21,963 (43.91) | .95 |
| 1 | 8893 (35.83) | 18,030 (36.05) | |
| 2 | 3222 (12.98) | 6449 (12.89) | |
| ≥3 | 1783 (7.18) | 3575 (7.15) | |
| SEIFA quintile, n (%) | |||
| 1 – Most disadvantaged | 5512 (22.21) | 10,941 (21.87) | .0040 |
| 2 | 3575 (14.41) | 7396 (14.73) | |
| 3 | 6097 (24.57) | 11,940 (23.87) | |
| 4 | 5562 (22.41) | 11,070 (22.13) | |
| 5 – Most advantaged | 4071 (16.40) | 8697 (17.39) | |
| Maternity service level a | |||
| Level 4 | 7199 (29.05) | 14,578 (29.19) | |
| Level 5 | 4931 (19.90) | 10,256 (20.54) | .01 |
| Level 6 | 12,531 (50.57) | 24,926 (49.91) |
a Level 6 maternity services provide regional or statewide specialized care for high-risk pregnancies, including extremely preterm births, and local care for all women and babies; Level 5 services care for normal- to moderate-risk pregnancies and manage labor and birth from 31 weeks gestation; Level 4 services provide local care for women and babies at normal and moderate risk, including planned births from 34 weeks gestation.
| Outcomes | Exposed | Control | aOR a | |||
|---|---|---|---|---|---|---|
| (n=24,817) | (n=50,017) | aOR | L | U | P value | |
| Stillbirths | ||||||
| Total | 85 (0.34) | 125 (0.25) | 1.37 | 1.04 | 1.81 | .03 |
| Preterm birth <37 wk | ||||||
| Total | 1471 (5.93) | 3117 (6.23) | 0.94 | 0.88 | 1.00 | .06 |
| Spontaneous | 667 (2.69) | 1408 (2.82) | 0.95 | 0.87 | 1.05 | .32 |
| Iatrogenic | 804 (3.24) | 1709 (3.42) | 0.94 | 0.86 | 1.02 | .13 |
| Preterm birth <32 wk | ||||||
| Total | 234 (0.94) | 476 (0.95) | 0.98 | 0.84 | 1.15 | .81 |
| Spontaneous | 98 (0.39) | 212 (0.42) | 0.93 | 0.73 | 1.18 | .54 |
| Iatrogenic | 136 (0.55) | 264 (0.53) | 1.03 | 0.83 | 1.26 | .81 |
| Preterm birth <28 wk | ||||||
| Total | 75 (0.30) | 154 (0.31) | 0.98 | 0.74 | 1.29 | .87 |
| Spontaneous | 34 (0.14) | 74 (0.15) | 0.93 | 0.62 | 1.39 | .72 |
| Iatrogenic | 41 (0.17) | 80 (0.16) | 1.03 | 0.70 | 1.50 | .89 |
| Newborn outcomes | ||||||
| Apgar score < 7 at 5 min | 354 (1.43) | 758 (1.58) | 0.97 | 0.87 | 1.09 | .63 |
| Fetal growth restriction | 493 (2.00) | 1010 (2.02) | 0.99 | 0.89 | 1.10 | .84 |
| SCN admission | 2851 (11.53) | 6242 (12.51) | 0.90 | 0.86 | 0.95 | <.0001 |
| NICU admission | 551 (2.23) | 1113 (2.23) | 0.99 | 0.89 | 1.10 | .88 |
| Pregnancy care indicators | ||||||
| First antenatal visit < 12 wk | 18,474 (74.44) | 29,488 (58.96) | 2.04 | 1.98 | 2.12 | <.0001 |
| Born before arrival | 142 (0.57) | 248 (0.50) | 1.17 | 0.95 | 1.45 | .13 |
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