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Objectives: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS)., Methods: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications., Results: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70)., Conclusions: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Head position during care may affect cerebral haemodynamics and contribute to the development of germinal matrix-intraventricular haemorrhage (GM-IVH) in very preterm infants. Turning the head toward one side may occlude jugular venous drainage while increasing intracranial pressure and cerebral blood volume. It is suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the infant is cared for in the supine 'head midline' position., Objectives: To assess whether head midline position is more effective than other head positions for preventing (or preventing extension) of GM-IVH in very preterm infants (< 32 weeks' gestation at birth)., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 12 September 2019), Embase (1980 to 12 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 12 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles., Selection Criteria: Randomised controlled trials (RCTs) comparing caring for very preterm infants in a supine head midline position versus a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of haemorrhage in a subgroup of infants. We planned to analyse horizontal (flat) versus head elevated positions separately for all body positions., Data Collection and Analysis: We used standard methods of Cochrane Neonatal. For each of the included trials, two review authors independently extracted data and assessed risk of bias. The primary outcomes were GM-IVH, severe IVH, and neonatal death. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence., Main Results: Three RCTs, with a total of 290 infants (either < 30 weeks' gestational age or < 1000 g body weight), met the inclusion criteria. Two trials compared supine midline head position versus head rotated 90° with the cot flat. One trial compared supine midline head position versus head rotated 90° with the bed tilted at 30°. We found no trials that compared supine versus prone midline head position. Meta-analysis of three trials (290 infants) did not show an effect on rates of GM-IVH (RR 1.11, 95% confidence interval (CI) 0.78 to 1.56; I² = 0%) and severe IVH (RR 0.71, 95% CI 0.37 to 1.33; I² = 0%). Neonatal mortality (RR 0.49, 95% CI 0.25 to 0.93; I² = 0%; RD -0.09, 95% CI -0.16 to -0.01) and mortality until hospital discharge (typical RR 0.50, 95% CI 0.28 to 0.90; I² = 0%; RD -0.10, 95% CI -0.18 to -0.02) were lower in the supine midline head position. The certainty of the evidence was very low for all outcomes because of limitations in study design and imprecision of estimates. We identified one ongoing study., Authors' Conclusions: We found few trial data on the effects of head midline position on GM-IVH in very preterm infants. Although meta-analyses suggest that mortality might be reduced, the certainty of the evidence is very low and it is unclear whether any effect is due to cot tilting (a co-intervention in one trial). Further high-quality RCTs would be needed to resolve this uncertainty., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Importance: Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation., Objective: To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping., Design, Setting, and Participants: Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018., Interventions: Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238)., Main Outcomes and Measures: The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin., Results: Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, -2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002)., Conclusions and Relevance: In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions., Trial Registration: ClinicalTrials.gov Identifier: NCT03019367.

Aim: To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?', Methods: MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles., Results: A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice., Conclusion: There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: It has been established that delayed umbilical cord clamping in preterm infants results in improvement in neonatal anemia, need for transfusion, incidence of necrotizing enterocolitis, and intraventricular hemorrhage by increasing neonatal circulating blood volume. However, the effects of umbilical cord milking as an alternative to delayed clamping in preterm infants are unclear., Objective: The primary objective of this study was to compare the effect of delayed clamping vs milking of the umbilical cord on the initial hematocrit concentration in preterm births (23-34 weeks gestation). In addition, we sought to compare the effects of delayed clamping vs milking on the incidences of intraventricular hemorrhage, necrotizing enterocolitis, and need for transfusion (secondary objectives)., Study Design: The study was an unblinded randomized controlled trial of singleton preterm infants who were born 23 weeks 0 days to 34 weeks 6 days gestation and were assigned to 1 of 2 controlled study groups: delayed cord clamping for 60 seconds or milking of the cord towards the infant 4 times before clamping. Randomization occurred via block randomization with an allocation ratio of 1 to 1. The patients' third stage of delivery was standardized for route of delivery and randomization arm. All comparisons were preformed with an intent-to-treat analysis approach. The study was powered at 80% with a probability value of .05 for the primary outcome measure of a hematocrit difference of 3% between the 2 groups., Results: Of the 204 randomized patients, 104 were assigned to the delayed subgroup, and 100 were assigned to the milking subgroup. There were no significant differences in baseline maternal characteristics noted between groups. Though there was not any statistically significant difference in neonatal outcomes between the cord clamping and milking groups, the occurrences of transfusion (15.5% vs 9.1%; P=.24), necrotizing enterocolitis (5.8% vs 3.0%; P=.49), and intraventricular hemorrhage (15.5% vs 10.1%; P=.35) were all lower in the milking group. The milking group had higher initial hematocrit concentration compared with the delayed clamping group, although this was not significant (51.8 [6.2%] vs 49.9 [7.7%]; P=.07]. Peak bilirubin levels and need for phototherapy were similar between groups., Conclusion: This study demonstrates that milking the umbilical cord may be an acceptable alternative to delayed cord clamping because there were similar effects on neonatal hematocrit concentrations and the need for neonatal transfusions and no increased risk for complications or neonatal morbidity. The present data support the concept that milking of the umbilical cord may offer an efficient and timely method of providing increased blood volume to the infant., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In a project to carefully observe and minimize risk factors of intraventricular hemorrhages (IVH) in preterm infants, the incidence decreased markedly at the perinatal Center in Ulm, Germany. By comparing its data with the perinatal center in Leipzig, Germany, we sought to identify what improvements could still be made., Methods: A retrospective survey was performed, including 189 infants from Leipzig and 89 from Ulm, all of whom weighed less than 1000 grams. A comparison between both perinatal centers was made., Results: IVH was more frequently detected in Leipzig (28.4%) than in Ulm (14.6%, p=0.011), yet only the incidence of mild IVH (grade 1-2) was affected since the incidence of severe IVH did not differ between the 2 centers (p=0.59, Leipzig 6.1%, Ulm 4.5%). Furthermore, several potentially avoidable risk factors of IVH were differentially distributed between the 2 centers. For example, postnatal hypocapnia and postnatal hypothermia occurred with higher frequency in Leipzig than in Ulm. Conversely, rapid postnatal application of surfactant was the rule in Leipzig but not in Ulm. Furthermore, sodium bicarbonate application occurred more frequently in Ulm., Conclusion: Both centers avoided certain risk factors for IVH with varying success. These results allow both centers to specifically target the risk factors that occurred with greater frequency to further reduce the incidence of IVH., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To determine the association between SpO 2 at 5 min and preterm infant outcomes., Design: Data from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher (≥0.6) initial inspiratory fractions of oxygen (FiO 2 ) for resuscitation, were examined., Setting: Individual patient analysis of 8 RCTs INTERVENTIONS: Lower (≤0.3) versus higher (≥0.6) oxygen resuscitation strategies targeted to specific predefined SpO 2 before 10 min of age., Patients: Infants <32 weeks gestation., Main Outcome Measures: Relationship between SpO 2 at 5 min, death and intraventricular haemorrhage (IVH) >grade 3., Results: 5 min SpO 2 data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO 2 study targets and 323 (46%) did not reach SpO 2 80%. Pooled data showed decreased likelihood of reaching SpO 2 80% if resuscitation was initiated with FiO 2 <0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO 2 <80% was associated with lower heart rates (mean difference -8.37, 95% CI -15.73 to -1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO 2 80%., Conclusion: Not reaching SpO 2 80% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval., Design: EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation., Setting: All French maternity units, except in a single administrative region, between March and December 2011., Population: A total of 750 twin neonates born between 24 and 31 weeks of gestation., Methods: Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment., Main Outcome Measures: Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes., Results: Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1-0.5), in-hospital mortality (0.3; 0.1-0.6), and the composite indicator (0.1; 0.1-0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3-1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course., Conclusion: In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days., Tweetable Abstract: A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24-31 weeks)., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Aim: To assess the effects of differential exposure to antenatal corticosteroid (ACS) on short- and long-term outcomes of infants born before 24 weeks of gestation., Methods: This is a retrospective cohort study of 147 infants delivered by 116 women at 21-23 weeks of gestation between January 2001 and December 2016 at a tertiary referral hospital in Seoul, Korea. Eligible subjects were categorized into the following three groups according to ACS exposure: non-user (n = 53), partial-course (n = 44), and complete-course (n = 50). Univariable and multivariable analyses were used to compare neonatal mortality, neonatal morbidities including intraventricular hemorrhage (IVH), and neurodevelopmental impairment including cerebral palsy among the three groups., Results: Neonatal mortality rate was significantly lower in the ACS-user groups (non-user, 52.8%; partial-course, 27.3%; complete-course, 28.0%; P = 0.01), but complete-course of ACS therapy had no advantages over partial-course. A lower incidence of IVH was observed in the complete-course group (non-users, 54.8%; partial-course, 48.6%; complete-course, 20.5%; P = 0.003). Multiple logistic regression analysis showed that ACS therapy, either partial- or complete-course, was associated with a lower rate of neonatal mortality (adjusted odds ratio (aOR) 0.375; 95% confidence interval (CI) 0.141-0.996 in partial-course; aOR 0.173; 95% CI 0.052-0.574) in complete-course). IVH (aOR 0.191; 95% CI 0.071-0.516) was less likely to occur in the complete-course group than in the non-user group. Neurodevelopmental impairment of survivors at 18-22 month after birth was not significantly different among the three groups., Conclusion: ACS therapy in preterm births at 21-23 weeks of gestation was associated with significantly reduced rates of neonatal mortality and IVH, especially with complete administration., Competing Interests: The authors have declared that no competing interests exist.

Objectives: For very preterm births, to compare alternative policies for umbilical cord clamping and immediate neonatal care., Design: Parallel group randomised (1:1) trial, using sealed opaque numbered envelopes., Setting: Eight UK tertiary maternity units., Participants: 261 women expected to have a live birth before 32 weeks, and their 276 babies., Interventions: Cord clamping after at least 2 min and immediate neonatal care with cord intact, or clamping within 20 s and immediate neonatal care after clamping., Main Outcome Measures: Intraventricular haemorrhage (IVH), death before discharge., Results: 132 women (137 babies) were allocated clamping ≥2 min and neonatal care cord intact, and 129 (139) clamping ≤20 s and neonatal care after clamping; six mother-infant dyads were excluded (2, 4) as birth was after 35 +6 weeks, one withdrew (death data only available) (0, 1). Median gestation was 28.9 weeks for those allocated clamping ≥2 min, and 29.2 for those allocated clamping ≤20 s. Median time to clamping was 120 and 11 s, respectively. 7 of 135 infants (5.2%) allocated clamping ≥2 min died and 15 of 135 (11.1%) allocated clamping ≤20 s; risk difference (RD) -5.9% (95% CI -12.4% to 0.6%). Of live births, 43 of 134 (32%) had IVH vs 47 of 132 (36%), respectively; RD -3.5% (-14.9% to 7.8%). There were no clear differences in other outcomes for infants or mothers., Conclusions: This is promising evidence that clamping after at least 2 min and immediate neonatal care with cord intact at very preterm birth may improve outcome; a large trial is urgently needed., Trial Registration: ISRCTN 21456601., Competing Interests: Competing interests: All authors declare no support from any organisation for the submitted work other than the NIHR programme grant; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; the grant funded research included development of a neonatal resuscitation trolley now marketed as ‘LifeStart’ and purchased by two sites for use in this trial, several authors were involved in development of the trolley but have no further relationship with the manufacturer; no other relationships or activities that could appear to have influenced the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To determine the association between antenatal steroids administration and intraventricular hemorrhage rates., Methods: We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007 to 2013 for infants ⩽32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age., Results: In 25 979 very-low-birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio=0.68, 95% confidence interval: 0.62, 0.75) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio=0.51, 95% confidence interval: 0.45, 0.58). This association was seen across gestational ages ranging from 22 to 29 weeks., Conclusions: Although current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age.