Abstract
Background
Preterm birth is the leading cause of neonatal mortality and morbidity worldwide. Very preterm neonates born between 23 + 0 and 31 + 6 weeks of gestational age are at particularly high risk due to complications requiring immediate intervention. Whether the differential organization of healthcare services during working hours (full staffing) versus off-hours (on-call) affects neonatal outcomes remains debated. This study aims to evaluate the effect of in-hours versus off-hours birth timing on early morbidity and mortality in very preterm neonates.
Methods
This was a single-center, retrospective cohort study conducted in a tertiary neonatal intensive care unit between January 1, 2014 and December 31, 2021. A total of 326 very preterm neonates born between 23 + 0 and 31 + 6 weeks of gestational age were included. Neonates were divided into two groups according to birth timing: Group 1 (In-hours: 08:00–17:00 on weekdays) and Group 2 (Off-hours: 17:01–07:59 on weekdays, weekends, and public holidays). Demographic data and neonatal outcomes were compared between groups, and risk factors for mortality were examined using multivariate logistic regression analysis.
Results
No statistically significant difference was found between groups regarding gestational age, birth weight, or in-hospital mortality (Group 1: 25.3% vs. Group 2: 23.2%, p = 0.658). However, maternal risk factors such as gestational hypertension (p = 0.005) and placental insufficiency (p = 0.001) were significantly higher in the in-hours group. In multivariate analysis, low 5-minute Apgar scores and advanced-stage NEC (stage ≥ 3 A) were identified as independent risk factors for mortality in both groups. Advanced-stage NEC showed a high odds ratio in both cohorts, though accompanied by wide confidence intervals due to small event sizes.
Conclusions
Birth timing (in-hours versus off-hours) had no significant effect on overall mortality or major morbidity in very preterm neonates, reflecting the continuity of care standards at our center. Advanced-stage NEC remained a critical predictor of mortality across both groups, independent of birth timing.
Keywords: Preterm birth, Off-hours birth, Neonatal mortality, Necrotizing enterocolitis, Weekend effect
Introduction
Preterm birth is the leading cause of neonatal mortality and morbidity worldwide, with the incidence of adverse outcomes increasing markedly as gestational age decreases [1]. Very preterm neonates born between 23 + 0 and 31 + 6 weeks of gestational age represent the most vulnerable population, facing life-threatening complications including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD) [2]. These complications can progress rapidly from the first hours of life and require immediate specialist intervention.
Whether the time of birth — during or outside working hours — influences neonatal outcomes has long been investigated within the framework of the so-called “weekend effect” [3]. While full staffing and immediate access to support services are available during working hours, the number of specialist physicians and the capacity for rapid intervention are known to be relatively reduced even in tertiary care centers during off-hours periods [4, 5]. This organizational difference is expected to affect clinical outcomes in the vulnerable preterm population. However, the literature presents conflicting findings: some studies report increased mortality risk associated with off-hours birth [4], whereas large multicenter analyses and studies conducted in tertiary centers with standardized care protocols have shown that this difference disappears [5, 10, 11].
The aim of this study was to evaluate the effect of in-hours (weekdays 08:00–17:00) versus off-hours (weekdays 17:01–07:59, weekends, and public holidays) birth timing on early morbidity and mortality in very preterm neonates born between 23 + 0 and 31 + 6 weeks of gestational age at a tertiary neonatal intensive care unit between 2014 and 2021, using a large eight-year cohort. Our hypothesis was to test whether the “weekend effect” can be overcome in a center providing continuous 24/7 specialist care.
Methods
Study design and setting
This was a single-center, retrospective cohort study conducted at the Neonatal Intensive Care Unit (NICU) of Trakya University between January 1, 2014 and December 31, 2021. The study protocol was approved by the local ethics committee (Trakya University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee; Decision No: TUTF-BAEK 2021/149, Date: 26.04.2021). The study was conducted in accordance with the principles of the Declaration of Helsinki and reported in compliance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
Participants
A total of 414 neonates admitted to the NICU during the study period were evaluated. Twenty-five cases with a diagnosis of major congenital anomaly or chromosomal abnormality and 63 cases with incomplete data in the medical records were excluded. A total of 326 neonates meeting the inclusion criteria of 23 + 0–31 + 6 weeks of gestational age were included in the analysis.
Grouping and variables
Neonates were divided into two groups according to birth timing:
Group 1 (In-hours): Births occurring on weekdays between 08:00 and 17:00 (n = 158).
Group 2 (Off-hours): Births occurring on weekdays between 17:01 and 07:59, on weekends, and on public holidays (n = 168).
Maternal (age, gestational hypertension, pre-eclampsia, chorioamnionitis, placental insufficiency, antenatal steroids), natal (mode of delivery, 5-minute Apgar score, need for resuscitation), and postnatal variables were recorded. The primary outcome was in-hospital mortality. Secondary outcomes included respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL/cPVL), retinopathy of prematurity (ROP), sepsis, need for mechanical ventilation (MV) and CPAP, duration of total parenteral nutrition (TPN), and total length of hospital stay. BPD was defined as the need for supplemental oxygen beyond 36 weeks postmenstrual age. NEC was staged according to the modified Bell criteria [6], IVH according to the Papile classification [7], and ROP according to the ICROP criteria [8].
Statistical analysis
Data were analyzed using IBM SPSS version 26.0. Categorical variables were expressed as frequency (n) and percentage (%). Continuous variables with normal distribution were presented as mean ± standard deviation (SD), and those without normal distribution as median (minimum–maximum). For between-group comparisons, the chi-square test or Fisher’s exact test was used for categorical variables, and the independent samples t-test or Mann-Whitney U test was used for continuous variables, depending on the distribution. Multivariate logistic regression analysis was performed to identify independent risk factors for mortality. Statistical significance was set at p < 0.05.
Results
Of the 326 very preterm neonates included in the study, 158 (48.5%) were born during in-hours and 168 (51.5%) during off-hours.
Demographic characteristics
No statistically significant difference was found between groups regarding mean gestational age (Group 1: 28.41 ± 2.65 weeks; Group 2: 28.47 ± 2.48 weeks), birth weight (Group 1: 1113.0 ± 400.9 g; Group 2: 1186.5 ± 399.5 g), sex distribution, or SGA rate (Table 1).
Table 1.
Demographic characteristics
| Variable | Group 1 — In-hours (n = 158) | Group 2 — Off-hours (n = 168) | p Value |
|---|---|---|---|
| Sex (male), n (%) | 74 (46.8) | 88 (52.4) | 0.317 |
| Gestational age (mean ± SD), weeks | 28.41 ± 2.65 | 28.47 ± 2.48 | 0.836 |
| Birth weight (mean ± SD), grams | 1113.0 ± 400.9 | 1186.5 ± 399.5 | 0.099 |
| SGA, n (%) | 60 (38.0) | 51 (30.4) | 0.266 |
Prenatal characteristics
Among prenatal variables, the rates of gestational hypertension (Group 1: 29.1% vs. Group 2: 16.1%; p = 0.005) and placental insufficiency (Group 1: 42.4% vs. Group 2: 24.4%; p = 0.001) were significantly higher in Group 1. No significant differences were observed between groups regarding other prenatal risk factors (pre-eclampsia, chorioamnionitis, PROM, antenatal steroids) (Table 2).
Table 2.
Prenatal characteristics
| Variable | Group 1 — In-hours (n = 158) | Group 2 — Off-hours (n = 168) | p Value |
|---|---|---|---|
| Maternal age (mean ± SD), years | 28.0 ± 6.51 | 28.1 ± 5.81 | 0.904 |
| Primigravida, n (%) | 87 (55.1) | 79 (47.0) | 0.147 |
| Multiple pregnancy, n (%) | 44 (27.8) | 44 (26.2) | 0.736 |
| Smoking, n (%) | 20 (12.7) | 34 (20.2) | 0.066 |
| Chronic hypertension, n (%) | 4 (2.5) | 5 (3.0) | > 0.999 |
| Gestational hypertension, n (%) | 46 (29.1) | 27 (16.1) | 0.005 |
| Gestational diabetes mellitus, n (%) | 14 (8.9) | 11 (6.5) | 0.565 |
| Eclampsia, n (%) | 1 (0.6) | 4 (2.4) | 0.372 |
| Pre-eclampsia, n (%) | 44 (27.8) | 32 (19.0) | 0.060 |
| HELLP syndrome, n (%) | 5 (3.2) | 1 (0.6) | 0.111 |
| Placental insufficiency, n (%) | 67 (42.4) | 41 (24.4) | 0.001 |
| Premature rupture of membranes, n (%) | 42 (26.6) | 56 (33.3) | 0.184 |
| Chorioamnionitis, n (%) | 15 (9.5) | 19 (11.3) | 0.723 |
| Antepartum hemorrhage, n (%) | 37 (23.4) | 48 (28.6) | 0.289 |
| Antenatal steroids, n (%) | 93 (58.9) | 94 (56.0) | 0.596 |
Natal characteristics
When natal characteristics were compared, the rate of vaginal delivery was significantly higher in Group 2 (Group 1: 8.2% vs. Group 2: 18.5%; p = 0.007). However, no significant difference was found between groups regarding 5-minute Apgar score (Group 1: 8 [IQR 6–9] vs. Group 2: 8 [IQR 5–9]; p = 0.612) or need for resuscitation (Table 3).
Table 3.
Natal characteristics
| Variable | Group 1 — In-hours (n = 158) | Group 2 — Off-hours (n = 168) | p Value |
|---|---|---|---|
| Vaginal delivery, n (%) | 13 (8.2) | 31 (18.5) | 0.007 |
| Cesarean section, n (%) | 145 (91.8) | 137 (81.5) | — |
| 5-min Apgar score, median (IQR) | 8 (6–9) | 8 (5–9) | 0.612 |
| Need for resuscitation, n (%) | 82 (51.9) | 94 (56.0) | 0.355 |
| — PPV, n (%) | 45 (28.5) | 51 (30.4) | — |
| — Advanced resuscitation, n (%) | 6 (3.8) | 20 (11.9) | — |
Neonatal morbidity and mortality
No statistically significant differences were found between groups in the incidence of RDS, BPD, PDA, NEC, IVH, ROP, or sepsis. Duration of TPN, need for CPAP and mechanical ventilation, and total length of hospital stay were also similar between groups. In-hospital mortality was 25.3% (n = 40) in Group 1 and 23.2% (n = 39) in Group 2, with no statistically significant difference between groups (p = 0.658) (Table 4).
Table 4.
Postnatal characteristics, morbidity, and mortality
| Variable | Group 1 — In-hours (n = 158) | Group 2 — Off-hours (n = 168) | p Value |
|---|---|---|---|
| Surfactant administration, n (%) | 52 (32.9) | 56 (33.3) | 0.814 |
| RDS, n (%) | 61 (38.6) | 67 (39.9) | 0.936 |
| BPD, n (%) | 18 (11.4) | 10 (6.0) | 0.120 |
| PDA, n (%) | 39 (24.7) | 32 (19.0) | 0.218 |
| NEC — all stages, n (%) | 77 (48.7) | 69 (41.1) | 0.244 |
| IVH — all stages, n (%) | 58 (36.7) | 59 (35.1) | 0.463 |
| PVL, n (%) | 3 (1.9) | 2 (1.2) | 0.676 |
| cPVL, n (%) | 5 (3.2) | 1 (0.6) | 0.111 |
| ROP — all stages, n (%) | 14 (8.9) | 17 (10.1) | 0.843 |
| Clinical sepsis, n (%) | 40 (25.3) | 43 (25.6) | 0.954 |
| Confirmed sepsis, n (%) | 18 (11.4) | 23 (13.7) | 0.647 |
| TPN duration (mean ± SD), days | 30.2 ± 26.6 | 28.0 ± 25.6 | 0.443 |
| CPAP therapy, n (%) | 68 (43.0) | 60 (35.7) | 0.620 |
| Mechanical ventilation, n (%) | 64 (40.5) | 59 (35.1) | 0.316 |
| Total length of stay (mean ± SD), days | 45.3 ± 38.1 | 42.2 ± 33.2 | 0.745 |
| Mortality, n (%) | 40 (25.3) | 39 (23.2) | 0.658 |
| Time to death (mean ± SD), days | 23.05 ± 37.87 | 22.87 ± 33.83 | 0.982 |
Mortality risk factors
Independent factors affecting mortality risk were examined using multivariate logistic regression analysis in both groups, and the results are presented in Table 5. Low 5-minute Apgar score was an independent predictor of mortality in both groups. Advanced-stage NEC (≥ 3 A) was associated with increased mortality risk in both groups, though the association was particularly strong in the off-hours group (Group 2: OR: 590.174; 95% CI: 8.457–41187.572; p = 0.003), with wide confidence intervals suggesting this should be interpreted with caution.
Table 5.
Independent risk factors for mortality in both groups (multivariate logistic regression)
| Variable | Group 1 (In-hours) | Group 2 (Off-hours) | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | p | OR | 95% CI | p | |
| Gestational week | 0.629 | 0.450–0.878 | 0.006* | 0.606 | 0.366–1.002 | 0.051 |
| 5-min Apgar score | 0.665 | 0.497–0.891 | 0.006* | 0.639 | 0.449–0.907 | 0.012* |
| NEC Stage ≥3 A | 16.962 | 1.011–284.451 | 0.049* | 590.174 | 8.457–41187.572 | 0.003* |
| ROP Stage ≥ 2 | 0.081 | 0.005–1.435 | 0.087 | 0.030 | 0.002–0.399 | 0.008* |
Other variables included in the analysis: maternal age, gestational hypertension (PIH), PROM, chorioamnionitis, multiple pregnancy, cesarean section, male sex, birth weight, SGA, BPD, IVH stage ≥ 3
OR Odds ratio, CI Confidence interval
*p < 0.05
Discussion
The primary finding of this study is that birth timing in-hours versus off-hours did not create a significant difference in overall mortality or major morbidity rates among very preterm neonates born between 23 + 0 and 31 + 6 weeks of gestational age at a tertiary care center. This finding is consistent with the continuous care model at our unit, in which the nurse-to-patient ratio (1:3 in both the intensive and intermediate care areas, and 1:2 in the isolation room unit) and the availability of a specialist neonatologist remain unchanged between day and night shifts. Notably, the significantly higher rates of gestational hypertension (29.1% vs. 16.1%; p = 0.005) and placental insufficiency (42.4% vs. 24.4%; p = 0.001) observed in the in-hours group most likely reflect the deliberate scheduling of high-risk deliveries during working hours, when full multidisciplinary support is immediately available. Although PIH was added to the multivariate model, it did not emerge as an independent predictor of mortality in either group (Group 1: OR = 0.863, p = 0.844; Group 2: OR = 0.094, p = 0.076), suggesting that its effect on mortality is mediated through other variables such as gestational age and mode of delivery rather than acting as a direct independent risk factor. This planned risk concentration in working hours is an important confounder that may have balanced outcome differences between groups [5].
The association between advanced-stage NEC (≥ 3 A) and mortality observed in the multivariate model warrants careful interpretation. NEC typically develops during the second or third week of postnatal life, well beyond the immediate perinatal period, and its pathogenesis is driven by intestinal immaturity, feeding practices, and microbial colonization rather than by the timing of birth itself [6]. Therefore, the observed association is unlikely to reflect a causal relationship between off-hours birth and NEC-related mortality. The very wide confidence interval (OR: 590.174; 95% CI: 8.457–41187.572) further underscores the statistical instability of this estimate, which is attributable to the small number of advanced-stage NEC events in the cohort. This finding should be regarded as an incidental observation rather than a primary conclusion of this study.
The inverse association between ROP stage ≥ 2 and mortality (OR: 0.030; p = 0.008) does not reflect a clinically protective effect of ROP, but rather arises from survival bias. Since ROP is typically diagnosed at 4–6 postnatal weeks, neonates who survive long enough to receive this diagnosis represent a more resilient subgroup that has already overcome the risk of early mortality.
A notable finding in the natal characteristics was the higher rate of advanced resuscitation in the off-hours group compared to the in-hours group (11.9% vs. 3.8%), although this difference did not reach statistical significance. This observation raises the question of whether the experience level of physicians and nurses attending deliveries outside working hours may differ from that during regular shifts a variable that was not formally measured in the present study. The requirement for advanced resuscitation is an immediate, time-sensitive event, and any reduction in the availability of experienced personnel during off-hours could theoretically affect initial stabilization, even when overall NICU care quality is maintained [3, 4]. This represents an important unmeasured confounder and should be addressed in future prospective studies.
It is important to recognize that the potential impact of birth timing on neonatal outcomes is likely limited to the immediate perinatal period specifically the quality of delivery room resuscitation, early stabilization, and the first hours of NICU admission. Events occurring later during the NICU stay, such as NEC, late-onset sepsis, or ROP, are primarily determined by postnatal factors including gestational maturity, nutrition, and infection control practices, and are not expected to be directly influenced by the hour of birth [9]. This biological consideration supports the interpretation that the absence of a weekend effect in our cohort reflects genuine equivalence of care across time periods, rather than simply an inability to detect a difference.
Lee et al. [3], reporting higher mortality with night-time births in a cohort of 5,192 neonates (24–32 weeks), noted that day and night nursing staffing were equal and attributed the mortality difference to a reduction in specialist physician numbers at night. Jensen et al. [4] found higher rates of BPD, IVH, and mortality in night-born neonates among 47,617 very low birth weight infants, demonstrating that severe IVH was an independent predictor of mortality. In contrast, Rocha et al. [5] (n = 220, < 30 weeks) found no significant difference in mortality between groups at their center, where a continuous care model was in place. Rizzolo et al. [9], in a large cohort (n = 173,789; 22–36 weeks), reported higher overall mortality in daytime births, while noting that night-time mortality was predominant only in the 22–27 week subgroup. Solis-Garcia et al. [10], in a multicenter study of 8,798 neonates (< 28 weeks), found no weekday/weekend mortality difference and attributed morbidity variations to differences in obstetric care and healthcare systems. The findings of our study are consistent with this latter group, supporting the view that the “weekend effect” can be overcome in centers providing standardized 24/7 specialist care.
From a broader perspective, Carty et al. [11] examined the relationship between birth timing and neonatal mortality in a retrospective cohort study covering 6,054,536 singleton live births in NHS maternity units in England between 2005 and 2014. After multivariate adjustment for maternal age, gestational age, birth weight, ethnicity, and obstetric risk factors, off-hours birth was not found to increase the risk of neonatal mortality due to asphyxia, anoxia, or birth trauma. This effect was significant only in term births (37–42 weeks) at the unadjusted analysis level and did not reach statistical significance in adjusted analyses. This finding is consistent with our study, supporting the notion that the “weekend effect” can be eliminated in centers providing 24/7 specialist care.
The role of staffing patterns in shaping neonatal outcomes has been increasingly recognized in the literature. Beltempo et al., in a multicenter retrospective cohort study of 1,870 infants born at 23–32 weeks across four level III NICUs, demonstrated that a higher nursing provision ratio in the first 24 h of admission was associated with lower odds of composite mortality or major morbidity (OR 0.93; 95% CI 0.89–0.98), while high unit occupancy independently increased the risk of adverse outcomes [12]. A systematic review similarly concluded that nurse-to-patient ratios appear to affect outcomes of neonatal intensive care, though limitations of the existing literature prevent clear conclusions about optimal staffing strategies [13]. Collectively, these findings suggest that the consistency of staffing across shifts rather than the time of birth per se may be the critical determinant of outcomes in very preterm neonates. The stable nurse-to-patient ratios maintained throughout the day and night at our center may therefore explain, at least in part, the absence of a weekend effect in our cohort.
Limitations
The main limitations of this study are as follows: the single-center and retrospective design limits the generalizability of the findings. The wide confidence interval of the OR calculated for rare but severe events such as NEC stage ≥3 A reflects statistical uncertainty arising from the sample size. Although the study covers a broad eight-year period, potential changes in clinical protocols or staffing structure during this time were not systematically evaluated. Furthermore, staffing patterns including the experience level of physicians and nurses attending deliveries and the availability of subspecialty support during off-hours were not systematically recorded. As these factors are highly facility-dependent, the findings of this study cannot be directly generalized to centers with different staffing models or organizational structures.
Conclusions
This study demonstrates that in a tertiary NICU with standardized 24/7 specialist coverage and consistent nurse-to-patient ratios, birth timing does not adversely affect mortality or major morbidity in very preterm neonates. These findings carry an important organizational implication: the weekend effect is not an inevitable consequence of off-hours birth, but rather a reflection of staffing and resource disparities that can be mitigated through deliberate institutional design.
From a policy perspective, our results support the development of formal guidelines mandating continuous specialist availability and standardized nurse-to-patient ratios in NICUs caring for very preterm infants, regardless of the time of day or day of the week. The higher rate of advanced resuscitation observed during off-hours, though not statistically significant, underscores the importance of ensuring that experienced personnel are consistently available at delivery, not only within the NICU itself. Additionally, the planned concentration of high-risk deliveries during working hours as reflected by the higher prevalence of gestational hypertension and placental insufficiency in the in-hours group represents a pragmatic risk-mitigation strategy that may contribute to equalized outcomes across time periods.
Collectively, findings from this study and similar future investigations may provide the evidence base needed to standardize minimum staffing requirements and specialist-to-patient ratios in neonatal intensive care units, ultimately contributing to the reduction of preventable mortality and morbidity in this vulnerable population. Future prospective multicenter studies with systematic documentation of staffing levels, personnel experience, and subspecialty availability across shifts are needed to identify the specific organizational factors that most strongly protect very preterm neonates from the adverse effects of birth timing.
Acknowledgements
We thank the nurses of the neonatal intensive care unit for their contributions during the data collection process.
Authors’ contributions
Tuğçe Lekesiz Erdur: Study design, data collection, statistical analysis, and drafting of the manuscript. Ahmet Erdur: Statistical analysis, data analysis, and manuscript revision. Betül A. Acunaş: Study supervision and final review. All authors have read and approved the final manuscript.
Funding
No specific funding was received from public, commercial, or not-for-profit funding bodies for this research.
Data availability
The datasets analyzed in this study are not publicly available due to patient confidentiality, but can be obtained from the corresponding author upon reasonable request and with the permission of the relevant institution.
Declarations
Ethics approval and consent to participate
This study was approved by the Non-Interventional Clinical Research Ethics Committee of Trakya University Faculty of Medicine (Decision Date/No: 26.04.2021, Decision No: 10/06 / TUTF-BAEK 2021/149).
The study was conducted in accordance with the principles of the Declaration of Helsinki. Due to its retrospective design, separate informed consent was waived by the ethics committee / permission for use of data was obtained from patient guardians within the scope of the general hospital admission consent.
Consent for publication
Not applicable. No personal data or photographs that could identify patients were used in this study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets analyzed in this study are not publicly available due to patient confidentiality, but can be obtained from the corresponding author upon reasonable request and with the permission of the relevant institution.