Search

Objective: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small‐for‐gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Design: Multicentre cohort study with nested randomised controlled trial (RCT). Setting: Nineteen secondary and tertiary care centres. Population: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Methods: Women were classified: (1) RCT‐eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below 35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT‐eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. Main outcome measures: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. Results: The cohort consisted of 690 women. The study was halted prematurely for low RCT‐inclusion rates (n = 40). In the RCT‐eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59–0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near‐significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre‐eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67–0.76). Conclusions: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34–36 weeks should only be performed in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). Methods: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. Results: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57–0.95; aOR 0.70, 95% CI 0.54–0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09–9.61; aOR 5.44, 95% CI 1.62–18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11–5.57). Conclusion: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI. [ABSTRACT FROM AUTHOR]

Background: Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function., Methods: We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV 1 ) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Standardised mean differences in FEV 1 and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies' FEV 1 effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework., Results: We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV 1 than controls (-0.58 sd, 95% CI -0.69- -0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4-3.4) for abnormal outcome, with high certainty of evidence. FEV 1 was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R 2 =36-96%)., Conclusion: This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence., Competing Interests: Conflict of interest: M. Königs reports grants from GSK, KNVB and Daan Theeuwes Center for Intensive Neurorehabilitation, payment or honoraria for lectures, presentations, manuscript writing or educational events from Vrije Universiteit Amsterdam and Applied University for Physiotherapy SOMT, and their partner has stock options in Open Up BV, a psychological care provider. All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Introduction: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality., Methods and Analysis: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach., Ethics and Dissemination: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21&#95;386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small-for-gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery., Design: Multicentre cohort study with nested randomised controlled trial (RCT)., Setting: Nineteen secondary and tertiary care centres., Population: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36 +6  weeks., Methods: Women were classified: (1) RCT-eligible: abnormal UCR twice consecutive and EFW below the 3 rd centile at/or below 35 weeks or below the 10 th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT-eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks., Main Outcome Measures: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity., Results: The cohort consisted of 690 women. The study was halted prematurely for low RCT-inclusion rates (n = 40). In the RCT-eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59-0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near-significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre-eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67-0.76)., Conclusions: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34-36 weeks should only be performed in the context of clinical trials., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years' corrected age (CA), and several BPD risk factors., Design: Single-centre historical cohort study with retrospective data collection., Setting: Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center., Patients: Preterm infants born at gestational age (GA) <30 weeks and surviving up to 36 weeks' postmenstrual age., Interventions: Perinatal characteristics, (social) demographics and comorbidities were collected from the electronic patient records., Main Outcome Measures: The primary outcomes were neurodevelopmental impairment (NDI) or late death, and respiratory morbidity at 2 and 5 years' CA. Using logistic regression and Brier scores, we investigated if the ordinal grade severity is associated with incremental increase of adverse long-term outcomes., Results: 584 preterm infants (median GA: 28.1 weeks) were included and classified according to the three BPD definitions. None of the definitions showed a clear ordinal incremental increase of risk for any of the outcomes with increasing severity classification. No significant differences were found between the three BPD definitions (Brier scores 0.169-0.230). Respiratory interventions, but not GA, birth weight or small for GA, showed an ordinal relationship with BPD severity in all three BPD definitions., Conclusion: The severity classification of three BPD definitions showed low accuracy of the probability forecast on NDI or late death and respiratory morbidity at 2 and 5 years' CA, with no differences between the definitions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal morbidity. Currently, there is no causal treatment, and management is focused on indicated preterm birth to prevent fetal death. Interest has risen in interventions that aim to improve placental function by administration of pharmacological agents affecting the nitric oxide pathway causing vasodilatation., Objectives: The objective of this systematic review and aggregate data meta-analysis is to assess the beneficial and harmful effects of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or different drugs affecting this pathway against each other, in pregnant women with severe early-onset FGR., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 July 2022), and reference lists of retrieved studies., Selection Criteria: We considered all randomised controlled comparisons of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or another drug affecting this pathway in pregnant women with severe early-onset FGR of placental origin, for inclusion in this review., Data Collection and Analysis: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis., Main Results: We included a total of eight studies (679 women) in this review, all of which contributed to the data and analysis. The identified studies report on five different comparisons: sildenafil compared with placebo or no therapy, tadalafil compared with placebo or no therapy, L-arginine compared with placebo or no therapy, nitroglycerin compared with placebo or no therapy and sildenafil compared with nitroglycerin. The risk of bias of included studies was judged as low or unclear. In two studies the intervention was not blinded. The certainty of evidence for our primary outcomes was judged as moderate for the intervention sildenafil and low for tadalafil and nitroglycerine (due to low number of participants and low number of events). For the intervention L-arginine, our primary outcomes were not reported. Sildenafil citrate compared to placebo or no therapy (5 studies, 516 women) Five studies (Canada, Australia and New Zealand, the Netherlands, the UK and Brazil) involving 516 pregnant women with FGR were included. We assessed the certainty of the evidence as moderate. Compared with placebo or no therapy, sildenafil probably has little or no effect on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.80 to 1.27, 5 studies, 516 women); may reduce fetal mortality (RR 0.82, 95% CI 0.60 to 1.12, 5 studies, 516 women), and increase neonatal mortality (RR 1.45, 95% CI 0.90 to 2.33, 5 studies, 397 women), although the results are uncertain for fetal and neonatal mortality as 95% confidence intervals are wide crossing the line of no effect. Tadalafil compared with placebo or no therapy (1 study, 87 women) One study (Japan) involving 87 pregnant women with FGR was included. We assessed the certainty of the evidence as low. Compared with placebo or no therapy, tadalafil may have little or no effect on all-cause mortality (risk ratio 0.20, 95% CI 0.02 to 1.60, one study, 87 women); fetal mortality (RR 0.11, 95% CI 0.01 to 1.96, one study, 87 women); and neonatal mortality (RR 0.89, 95% CI 0.06 to 13.70, one study, 83 women). L-Arginine compared with placebo or no therapy (1 study, 43 women) One study (France) involving 43 pregnant women with FGR was included. This study did not assess our primary outcomes. Nitroglycerin compared to placebo or no therapy (1 studies, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. Sildenafil citrate compared to nitroglycerin (1 study, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups., Authors' Conclusions: Interventions affecting the nitric oxide pathway probably do not seem to influence all-cause (fetal and neonatal) mortality in pregnant women carrying a baby with FGR, although more evidence is needed. The certainty of this evidence is moderate for sildenafil and low for tadalafil and nitroglycerin. For sildenafil a fair amount of data are available from randomised clinical trials, but with low numbers of participants. Therefore, the certainty of evidence is moderate. For the other interventions investigated in this review there are insufficient data, meaning we do not know whether these interventions improve perinatal and maternal outcomes in pregnant women with FGR., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: The use of low-dose aspirin by pregnant women to prevent preterm pre-eclampsia is gradually increasing. The administration of aspirin during pregnancy improves perinatal outcome, which could translate into improved child outcome in the long term. However, antenatal exposure to aspirin could have adverse effects on child development that may manifest later in life. The aim of this follow-up study is to assess the long-term effects of antenatal exposure to low-dose aspirin compared with placebo on survival, (neuro)development, behaviour and general health at 4 years corrected age., Methods and Analysis: This is a follow-up study of the Dutch double-blind randomised controlled APRIL trial which assessed the effectiveness of treatment with aspirin (80 mg daily) compared with placebo for the prevention of preterm birth in women with a previous spontaneous preterm birth. Treatment was initiated before 16 weeks of gestation and continued until 36 weeks or birth. We aim to follow-up all 379 children born to women who participated in the APRIL trial and survived the neonatal period, at the corrected age of 4 years. The main outcomes are (neuro)development as assessed by the Ages and Stages Questionnaire, and behaviour as assessed by the Strength and Difficulties Questionnaire. Additional outcomes include mortality, growth and general health from birth up to 4 years, and a composite outcome including mortality, abnormal (neuro)development and problem behaviour. Analyses will be performed by intention-to-treat using a superiority design., Ethics and Dissemination: Institutional Review Board approval was obtained from the Medical Research Ethics Committee from Amsterdam Medical Center (no. W20 289#20.325). The results will be published in a peer-reviewed journal and presented at conferences., Trial Registration Number: The APRIL trial (NTR5675, NL5553; EudraCT number 2015-003220-31) and the APRIL follow-up study (NL8950) are registered in the Dutch trial register. The study is funded by the Amsterdam Reproduction & Development research institute., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The French EPIPAGE-2 study evaluated a large group of premature born children (24-34 weeks' gestational age (GA))) at age 5.5 years. Outcome information of the whole cohort was presented after careful imputation including/using the variable socio-economic-status (SES), because participation rate improved with increasing SES. Survival improved with increasing GA. Survival without moderate or severe impairment was 20% in children born at 24-26 weeks' GA, but among the survivors 75% had no or mild impairment. Mild cognitive impairment rates were comparable and common among all GA groups (25-28%) and thus frequent in prematures. School problems were also common. In addition to prematurity, SES is an important risk factor for developmental impairment. Follow-up programs for premature infants beyond 30 weeks' GA are less common and may need extra attention in low SES families. Future studies should focus on both prevention of prematurity and programs to improve outcome.