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Cesarean delivery is a common route of delivery before term, but the benefits or harms for preterm infants are still unknown. This review aimed to gather information on the current epidemiology of preterm cesarean delivery using data from international collaborations and on neonatal outcomes concerning the mode of delivery. Of note, 4 obstetrical scenarios were reviewed: preterm births with cephalic or noncephalic fetal presentations, preterm preeclampsia, and preterm birth of multiple pregnancies. In addition, cesarean delivery for preterm birth and its association with later child health was briefly discussed. In Europe, the highest cesarean delivery rates were reported in very preterm births (66%) and moderately preterm births (58%), with marked between-country variations. Among very preterm infants, international cesarean delivery rates averaged 70% at 28 to 31 weeks of gestation, with declining and more variable rates at lower gestational ages, especially at 22 and 23 weeks of gestation. In moderate preterm births (32–33 weeks of gestation) and late preterm births (34–36 weeks of gestation), country-specific cesarean delivery rates mirrored practice in the full-term population. In low-risk, singletons in cephalic position, primary cesarean delivery before term has been associated with a higher risk of neonatal respiratory morbidity than vaginal delivery, particularly among moderate-late preterm infants. However, preterm cesarean delivery for breech presentation (singleton and multiple pregnancies with the first fetus in noncephalic presentation) has been associated with lower neonatal mortality than vaginal delivery, particularly among very extremely preterm infants. The literature provided no clear and consistent support for the neonatal benefits of cesarean delivery vs a trial of induction of labor in preterm preeclampsia. The same was true for twin pregnancies, except for monoamniotic twin pregnancies that were recommended for primary cesarean delivery in moderately preterm gestations. There are associations between preterm cesarean delivery and adverse childhood health outcomes, but causality has not been established. With the exception of moderate and late preterm births, in which unnecessary, policy-dictated cesarean delivery could be reduced, there are usually strong medical indications for cesarean delivery in very or extremely preterm gestations. In such situations, the immediate benefits for the infant of increased chances of survival without severe neonatal morbidity should outweigh any long-term health issues. In conclusion, there is insufficient evidence to support routine delivery of preterm infants by cesarean delivery except for breech presentation, maternal or fetal emergencies, and monoamniotic twins.

Aim: We evaluated the increased centralisation of extremely preterm (EPT) births in Sweden in relation to the changes in mortality and morbidity.

Methods: Population-based data covering Swedish live births from 22 + 0 to 26 + 6 weeks of gestation during 2004–2007 and 2014–2016 were analysed for associations between time-period, birth within (inborn) or outside (outborn) regional centres, and outcomes.

Results: Among 1626 liveborn infants, 703 were born in 2004–2007 and 923 in 2014–2016. Birth outside (vs. within) regional centres was associated with a higher infant mortality even after adjustment for birth cohort, gestational age, birthweight standard deviation score and infant sex (adjusted odds ratio 2.01, 95% confidence interval 1.31–3.07, p = 0.001). The higher 1-year mortality in outborn infants was mainly due to more deaths within 24 h after birth. Outborn infants had a higher incidence of intraventricular haemorrhage grade 3–4 than inborn infants (22% vs. 14% in 2004–2007, and 22% vs. 13% in 2014–2016, both p < 0.05). While survival to 1 year without major morbidity increased in inborn infants (33%–40%, p = 0.008), it remained unchanged in outborn infants (29% vs. 30%, p = 0.88).

Conclusion: Centralisation of EPT births contributed to a lower 1-year mortality in 2014–2016 than that in 2004–2007, attributed to a decrease in deaths before 24 h among inborn infants.

Objective: To compare neurodevelopmental outcomes in extremely preterm (EPT) children born across two epochs in Sweden.

Design and setting: Nationwide population-based cohorts of infants born at 22–26 weeks’ gestation in 2004–2007 (Cohort 1) and 2014–2016 (Cohort 2), comprising 1606 live births. Survivors were assessed at 2–2.5 years’ corrected age using the same protocol design.

Main outcome: The primary outcome was neurodevelopmental impairment (NDI), defined as a composite of moderate–severe cerebral palsy (CP), visual or hearing deficits, or moderate–severe cognitive, language or motor impairment assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III). For children not assessed with Bayley-III, NDI was defined as moderate–severe speech delay, general developmental delay or categories of CP, vision and hearing impairment. Outcomes were compared using logistic regression to evaluate differences between cohorts and perinatal and socioeconomic risk factors.

Results: Of 1188 eligible survivors, 1062 (89.3%) were assessed (mean gestational age (GA) 24.8 weeks; 54.9% male). The prevalence of moderate–severe NDI at 22, 23, 24, 25 and 26 weeks’ gestation was 60% vs 52%, 51% vs 51%, 34% vs 42%, 27% vs 32% and 17% vs 24% in Cohorts 1 and 2, respectively. Overall prevalence did not differ significantly (27% vs 35%; adjusted OR (AOR) 1.2, 95% CI 0.94 to 1.6). Among 724 (68%) children assessed with Bayley III, Cohort 2 had higher rates of cognitive delay (21.6% vs 11.3%; AOR 1.8, 95% CI 1.1 to 3.4) and language delay (40.9% vs 16.1%; AOR 3.3, 95% CI 1.4 to 4.1). Low GA and maternal country of birth outside the Nordic region were the strongest predictors of NDI and cognitive delay, the latter association confined to Cohort 2.

Conclusion: Although survival of EPT infants in Sweden has improved, long-term neurodevelopmental outcomes have not. The root causes of failed improvements in long-term outcomes for EPT infants are complex and need further clarification.

Importance: Postnatal intensive care for preterm infants born at 22 to 23 weeks' gestation is increasing, although survival rates remain low. Information on outcomes for multiple countries or regions can be important for research, benchmarking, quality improvement, and parental counseling.

Objective: To evaluate survival and major morbidities and their between-network variations in infants born at 22 to 23 weeks' gestation in 11 neonatal networks participating in the International Network for Evaluation of Outcomes (iNeo) in neonates in 12 countries or regions.

Design, Setting, and Participants: International registry-based cohort study of infants born at 22 to 23 weeks' gestation from January 1, 2015, through December 31, 2021, without major congenital anomalies who were admitted for neonatal intensive care in 11 national or regional neonatal consortia. Data analysis was performed from December 2, 2023, to June 15, 2025.

Exposures: Neonatal consortium and gestational age at birth.

Main Outcomes and Measures: Survival to neonatal intensive care unit discharge, major neonatal morbidities, and survival without any major morbidities.

Results: A total of 5019 neonates were included (1084 of 4636 neonates [23%] with a maternal age >35 years; 2641 of 5017 neonates [53%] male); among them, 846 neonates were born at 22 weeks' gestation and 4173 were born at 23 weeks' gestation. Variations between contributing networks for perinatal management at 22 and 23 weeks' gestation, respectively, include any antenatal steroids (ranges of 18%-83% and 57%-98%), cesarean birth (0%-42% and 5%-73%), and outborn (0%-26% and 0%-22%). Significant variations between contributing networks for adjusted probabilities of outcomes at 22 and 23 weeks' gestation, respectively, include survival to discharge (95% CIs of 9%-64% and 16%-80%; P <.001), grade 3 or 4 periventricular hemorrhage (PVH) or periventricular leukomalacia (PVL) (severe PVH or PVL: 24%-65% and 18%-56%; P <.001), survival without severe PVH or PVL (7%-53% and 9%-69%; P <.001), treated retinopathy of prematurity among survivors (32%-57% [P =.008] and 16%-48% [P <.001]), bronchopulmonary dysplasia among survivors (for 23 weeks only: 64%-88%; P <.001), and necrotizing enterocolitis (for 23 weeks only: 6%-28%; P <.001). Standardized incidence ratios showed significant differences in survival and major morbidities in some networks compared with a reference population from all other networks.

Conclusions: Substantial international variations were identified in outcomes for infants born at 22 to 23 weeks' gestation who were admitted to 11 neonatal networks in the 12 countries or regions. The variations can be due to differences in systems, care practices, attitudes, and culture; however, identification of variation can help focus efforts toward research aimed at understanding the causal determinants of variation.

Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects.

Background: Our aim was to evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade.

Methods: Data from two Swedish population-based studies of live-born infants with gestational age (GA) 22–26 weeks, born during 2004–2007 (n=702) and 2014–2016 (n=885), were compared for survival, any BPD, moderate BPD and severe BPD and the composite outcomes of any BPD or death and severe BPD or death at 36 weeks postmenstrual age (PMA). Ventilation strategies and interventions were analysed. Any BPD was defined as the use of supplemental oxygen or any respiratory support at 36 weeks PMA, moderate BPD as nasal cannula with <30% oxygen and severe BPD as ≽30% oxygen, continuous positive airway pressure (CPAP) or mechanical ventilation.

Results: Survival to 36 weeks PMA increased from 72% to 81% (p<0.001). Total days on mechanical ventilation increased from a median of 9 to 16 days (p<0.001). High-flow nasal cannula (HFNC) was introduced between the cohorts, and days of CPAP and HFNC increased from 44 to 50 days (p<0.001). Any BPD was unchanged at 65% versus 68%. Moderate BPD increased from 37% to 47% (p=0.003), while the incidence of severe BPD decreased from 28% to 23% (p<0.046). Severe BPD or death decreased from 48% to 37% (p<0.001), while any BPD or death remained unchanged at 74% versus 75%.

Conclusion: Even though an increased survival of infants born at 22–26 weeks GA was accompanied by an increased duration of invasive and non-invasive respiratory support, the incidence of any BPD remained unchanged, while severe BPD decreased in infants alive at 36 weeks PMA.

Background: Neonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.

Aim: The aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.

Methods: In 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.

Results: In Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.

Conclusions: In this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.

DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records.

PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.

MAIN OUTCOME MEASURES: NEC incidence.

RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).

CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis.

Methods: We performed a retrospective populationbased cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Lateonset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network.

Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis.

Conclusions: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.

Objective: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.

Design/Setting: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions.

Main outcome: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined.

Results: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4).

Conclusion: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.