慶應義塾研究者情報データベース

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• Methylxanthine for preventing morbidity and mortality in preterm infants: a network meta-analysis

  Kinoshita M., Del Giovane C., Mitra S., Hall R., Soll R., Bruschettini M.

  Cochrane Database of Systematic Reviews （Cochrane Database of Systematic Reviews)  2023 （ 12 ）  2023年12月

  ISSN  14651858

  　概要を見る

  Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To determine the effects of methylxanthines (caffeine; theophylline or aminophylline) and 'no methylxanthine administration' on morbidity and mortality in preterm infants, using network meta-analysis.

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• Systemic opioid regimens for postoperative pain in neonates

  Kinoshita M., Borges do Nascimento I.J., Styrmisdóttir L., Bruschettini M.

  Cochrane Database of Systematic Reviews （Cochrane Database of Systematic Reviews)  2023 （ 1 ）  2023年01月

  ISSN  14651858

  　概要を見る

  Background: Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. Objectives: To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration. Search methods: Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry. Selection criteria: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration. Data collection and analysis: According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies. Main results: In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. Authors' conclusions: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.

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• Prenatal interventions for fetal growth restriction in animal models: A systematic review

  Valenzuela I., Kinoshita M., van der Merwe J., Maršál K., Deprest J.

  Placenta （Placenta)  126   90 - 113 2022年08月

  ISSN  01434004

  　概要を見る

  Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.

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• Opioids for procedural pain in neonates

  Kinoshita M., Olsson E., Borys F., Bruschettini M.

  Cochrane Database of Systematic Reviews （Cochrane Database of Systematic Reviews)  2021 （ 12 ）  2021年12月

  ISSN  14651858

  　概要を見る

  Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To determine the effects of opioid analgesics in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.

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• Extent of absent end-diastolic flow in umbilical artery and outcome of pregnancy

  Kinoshita M., Thuring A., Morsing E., Maršál K.

  Ultrasound in Obstetrics and Gynecology （Ultrasound in Obstetrics and Gynecology)  58 （ 3 ） 369 - 376 2021年09月

  ISSN  09607692

  　概要を見る

  Objective: To investigate if the extent of absent end-diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome. Methods: This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (Ta/Ttot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the Ta/Ttot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed. Results: A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163–279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320–3326 g) and deviation from expected birth weight (standard deviation score) was –2.975 (range, –6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the Ta/Ttot ratio in the total study group. Mean Ta/Ttot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively (P = 0.002). For fetuses examined before 30 weeks' gestation, a Ta/Ttot ratio cut-off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver-operating-characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66). Conclusions: In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth-restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision-making in very preterm growth-restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

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