多施設共同データベースを活用した周産期の診療に資するデータ分析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 岩中 督, 東京大学准教授 近藤 尚己, 東京大学講師 長野 宏一朗, 東京大学講師 土田 晋也, 東京大学講師 槇野 陽介University of Tokyo(東京大学

Comprehensive Assessment of Risk Factors of Cause-Specific Infant Deaths in Japan

Background: Public attention is given to infants with socially high risks of child abuse and neglect, while clinical attention is provided to infants with a biologically high risk of diseases. However, few studies have systematically evaluated how biological or social factors cross over and affect cause-specific infant mortality.Methods: We linked birth data with death data from the Japanese national vital statistics database for all infants born from 2003–2010. Using multivariate logistic regression, we examined the association between biological and social factors and infant mortality due to medical causes (internal causes), abuse (intentional external causes), and accidents (unintentional external causes).Results: Of 8,941,501 births, 23,400 (0.26%) infants died by 1 year of age, with 21,884 (93.5%) due to internal causes, 175 (0.75%) due to intentional external causes, and 1,194 (5.1%) due to unintentional external causes. Infants with high social risk (teenage mothers, non-Japanese mothers, single mothers, unemployed household, four or more children in the household, or birth outside of health care facility) had higher risk of death by intentional, unintentional, and internal causes. Infant born with small for gestational age and preterm had higher risks of deaths by internal and unintentional causes, but not by intentional causes.Conclusions: Both biological as well as social factors were associated with infant deaths due to internal and external causes. Interdisciplinary support from both public health and clinical-care professionals is needed for infants with high social or biological risk to prevent disease and injury

Brief Parenteral Nutrition Accelerates Weight Gain, Head Growth Even in Healthy VLBWs

Introduction: Whether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate. Methods: We studied 4005 hospitalized VLBW, very preterm (23–32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003–2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10th percentile for postmenstrual age) at discharge. Results: 40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates. Discussion Even in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants

Pre-pregnancy BMI-specific optimal gestational weight gain for women in Japan

Background: The Institute of Medicine (IOM) guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI) and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM) recommendations. Methods: We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005–2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0–18.4, 18.5–19.9, 20–22.9, 23–24.9, and 25–27.4 kg/m2), we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications) using multivariate regression. Results: Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks) for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m2, and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m2. Conclusion: Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m2 as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health

ObjectiveTo investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries.DesignSecondary analysis of a cross-sectional study.SettingTwenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health.Population29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour.MethodsWe compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age.Main Outcome MeasuresSevere maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality.ResultsOdds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age.ConclusionsElective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups

Zika virus infection in pregnancy: a systematic review of disease course and complications

OBJECTIVES: To characterize maternal Zika virus (ZIKV) infection and complement the evidence base for the WHO interim guidance on pregnancy management in the context of ZIKV infection. METHODS: We searched the relevant database from inception until March 2016. Two review authors independently screened and assessed full texts of eligible reports and extracted data from relevant studies. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) and the National Institute of Health (NIH) tool for observational studies and case series/reports, respectively. RESULTS: Among 142 eligible full-text articles, 18 met the inclusion criteria (13 case series/reports and five cohort studies). Common symptoms among pregnant women with suspected/confirmed ZIKV infection were fever, rash, and arthralgia. One case of Guillain-Barre syndrome was reported among ZIKV-infected mothers, no other case of severe maternal morbidity or mortality reported. Complications reported in association with maternal ZIKV infection included a broad range of fetal and newborn neurological and ocular abnormalities; fetal growth restriction, stillbirth, and perinatal death. Microcephaly was the primary neurological complication reported in eight studies, with an incidence of about 1% among newborns of ZIKV infected women in one study. CONCLUSION: Given the extensive and variable fetal and newborn presentations/complications associated with prenatal ZIKV infection, and the dearth of information provided, knowledge gaps are evident. Further research and comprehensive reporting may provide a better understanding of ZIKV infection in pregnancy and attendant maternal/fetal complications. This knowledge could inform the creation of effective and evidence-based strategies, guidelines and recommendations aimed at the management of maternal ZIKV infection. Adherence to current best practice guidelines for prenatal care among health providers is encouraged, in the context of maternal ZIKV infection

Unit-Level Variations in Healthcare Professionals' Availability for Preterm Neonates <29 Weeks' Gestation: An International Survey

INTRODUCTION The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHOD Online, pre-piloted questionnaires about the availability of healthcare professionals were sent to the directors of 390 tertiary neonatal units in 10 international networks: Australia/New Zealand, Canada, Finland, Illinois, Israel, Japan, Spain, Sweden, Switzerland, and Tuscany. RESULTS Overall, 325 of 390 units (83%) responded. About half of the units (48%; 156/325) cared for 11-30 neonates/day and had team-based (43%; 138/325) care models. Neonatologists were present 24 h a day in 59% of the units (191/325), junior doctors in 60% (194/325), and nurse practitioners in 36% (116/325). A nurse-to-patient ratio of 1:1 for infants who are unstable and require complex care was used in 52% of the units (170/325), whereas a ratio of 1:1 or 1:2 for neonates requiring multisystem support was available in 59% (192/325) of the units. Availability of a respiratory therapist (15%, 49/325), pharmacist (40%, 130/325), dietitian (34%, 112/325), social worker (81%, 263/325), lactation consultant (45%, 146/325), parent buddy (6%, 19/325), or parents' resource personnel (11%, 34/325) were widely variable between units. CONCLUSIONS We identified variability in the availability and organization of the healthcare professionals between and within countries for the care of extremely preterm neonates. Further research is needed to associate healthcare workers' availability and outcomes

Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study

BACKGROUND Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable

Birthweight of babies born to migrant mothers - What role do integration policies play?

Birthweights of babies born to migrant women are generally lower than those of babies born to native-born women. Favourable integration policies may improve migrants’ living conditions and contribute to higher birthweights. We aimed to explore associations between integration policies, captured by the Migrant Integration Policy Index (MIPEX), with offspring birthweight among migrants from various world regions. In this cross-country study we pooled 31 million term birth records between 1998 and 2014 from ten high-income countries: Australia, Belgium, Canada, Denmark, Finland, Japan, Norway, Spain, Sweden and United Kingdom (Scotland). Birthweight differences in grams (g) were analysed with regression analysis for aggregate data and random effects models. Proportion of births to migrant women varied from 2% in Japan to 28% in Australia. The MIPEX score was not associated with birthweight in most migrant groups, but was positively associated among native-born (mean birthweight difference associated with a 10-unit increase in MIPEX: 105 g; 95% CI: 24, 186). Birthweight among migrants was highest in the Nordic countries and lowest in Japan and Belgium. Migrants from a given origin had heavier newborns in countries where the mean birthweight of native-born was higher and vice versa. Mean birthweight differences between migrants from the same origin and the native-born varied substantially across destinations (70 g–285 g). Birthweight among migrants does not correlate with MIPEX scores. However, birthweight of migrant groups aligned better with that of the native-born in destination counties. Further studies may clarify which broader social policies support migrant women and have impacts on perinatal outcomes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Use of the Robson classification to assess caesarean section trends in 21 countries: a secondary analysis of two WHO multicountry surveys

Background: Rates of caesarean section surgery are rising worldwide, but the determinants of this increase, especially in low-income and middle-income countries, are controversial. In this study, we aimed to analyse the contribution of specific obstetric populations to changes in caesarean section rates, by using the Robson classification in two WHO multicountry surveys of deliveries in health-care facilities. The Robson system classifies all deliveries into one of ten groups on the basis of five parameters: obstetric history, onset of labour, fetal lie, number of neonates, and gestational age. Methods: We studied deliveries in 287 facilities in 21 countries that were included in both the WHO Global Survey of Maternal and Perinatal Health (WHOGS; 2004–08) and the WHO Multi-Country Survey of Maternal and Newborn Health (WHOMCS; 2010–11). We used the data from these surveys to establish the average annual percentage change (AAPC) in caesarean section rates per country. Countries were stratified according to Human Development Index (HDI) group (very high/high, medium, or low) and the Robson criteria were applied to both datasets. We report the relative size of each Robson group, the caesarean section rate in each Robson group, and the absolute and relative contributions made by each to the overall caesarean section rate. Findings: The caesarean section rate increased overall between the two surveys (from 26·4% in the WHOGS to 31·2% in the WHOMCS, p=0·003) and in all countries except Japan. Use of obstetric interventions (induction, prelabour caesarean section, and overall caesarean section) increased over time. Caesarean section rates increased across most Robson groups in all HDI categories. Use of induction and prelabour caesarean section increased in very high/high and low HDI countries, and the caesarean section rate after induction in multiparous women increased significantly across all HDI groups. The proportion of women who had previously had a caesarean section increased in moderate and low HDI countries, as did the caesarean section rate in these women. Interpretation: Use of the Robson criteria allows standardised comparisons of data across countries and timepoints and identifies the subpopulations driving changes in caesarean section rates. Women who have previously had a caesarean section are an increasingly important determinant of overall caesarean section rates in countries with a moderate or low HDI. Strategies to reduce the frequency of the procedure should include avoidance of medically unnecessary primary caesarean section. Improved case selection for induction and prelabour caesarean section could also reduce caesarean section rates