Chie Nagata

Vitamin C supplementation in pregnancy

BACKGROUNDnVitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy.nnnOBJECTIVESnTo evaluate the effects of vitamin C supplementation, alone or in combination with other separate supplements on pregnancy outcomes, adverse events, side effects and use of health resources.nnnSEARCH METHODSnWe searched the Cochrane Pregnancy and Childbirth Groups Trials Register (31 March 2015) and reference lists of retrieved studies.nnnSELECTION CRITERIAnAll randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.nnnMAIN RESULTSnTwenty-nine trials involving 24,300 women are included in this review. Overall, 11 trials were judged to be of low risk of bias, eight were high risk of bias and for 10 trials it was unclear. No clear differences were seen between women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control for the risk of stillbirth (risk ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants; 11 studies; I² = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI 0.58 to 1.08; 19,575 participants; 11 studies; I² = 0%), perinatal death (average RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I² = 35%), birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326 participants; 13 studies; I² = 69%), intrauterine growth restriction (RR 0.98, 95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I² = 15%; high quality evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250 participants; 16 studies; I² = 49%; high quality evidence), preterm PROM (prelabour rupture of membranes) (average RR 0.98, 95% CI 0.70 to 1.36; 16,825 participants; 10 studies; I² = 70%; low quality evidence), term PROM (average RR 1.26, 95% CI 0.62 to 2.56; 2674 participants; three studies; I² = 87%), and clinical pre-eclampsia (average RR 0.92, 95% CI 0.80 to 1.05; 21,956 participants; 16 studies; I² = 41%; high quality evidence).Women supplemented with vitamin C alone or in combination with other supplements compared with placebo or no control were at decreased risk of having a placental abruption (RR 0.64, 95% CI 0.44 to 0.92; 15,755 participants; eight studies; I² = 0%; high quality evidence) and had a small increase in gestational age at birth (MD 0.31, 95% CI 0.01 to 0.61; 14,062 participants; nine studies; I² = 65%), however they were also more likely to self-report abdominal pain (RR 1.66, 95% CI 1.16 to 2.37; 1877 participants; one study). In the subgroup analyses based on the type of supplement, vitamin C supplementation alone was associated with a reduced risk of preterm PROM (average RR 0.66, 95% CI 0.48 to 0.91; 1282 participants; five studies; I² = 0%) and term PROM (average RR 0.55, 95% CI 0.32 to 0.94; 170 participants; one study). Conversely, the risk of term PROM was increased when supplementation included vitamin C and vitamin E (average RR 1.73, 95% CI 1.34 to 2.23; 3060 participants; two studies; I² = 0%). There were no differences in the effects of vitamin C on other outcomes in the subgroup analyses examining the type of supplement. There were no differing patterns in other subgroups of women based on underlying risk of pregnancy complications, timing of commencement of supplementation or dietary intake of vitamin C prior to trial entry. The GRADE quality of the evidence was high for intrauterine growth restriction, preterm birth, and placental abruption, moderate for stillbirth and clinical pre-eclampsia, low for preterm PROM.nnnAUTHORS CONCLUSIONSnThe data do not support routine vitamin C supplementation alone or in combination with other supplements for the prevention of fetal or neonatal death, poor fetal growth, preterm birth or pre-eclampsia. Further research is required to elucidate the possible role of vitamin C in the prevention of placental abruption and prelabour rupture of membranes. There was no convincing evidence that vitamin C supplementation alone or in combination with other supplements results in other important benefits or harms.

Three suspected cases of sugammadex-induced anaphylactic shock

BackgroundSugammadex has a unique mechanism of action and is widely used because of its safety and efficacy. A few recent reports have described allergic reactions to clinical doses of sugammadex. We hereby describe another series of cases of possible anaphylaxis to sugammadex.Case presentationWe present three suspected cases of sugammadex-induced anaphylactic shock, including a 13-year-old boy who underwent laparoscopic appendectomy, a 75-year-old woman who underwent left knee arthroplasty, and a 34-year-old man who underwent left pansinectomy for sinobronchitis. All three patients received general anesthesia with rocuronium and their tracheas were intubated. Shortly after injection of sugammadex for reversal of rocuronium, all of them experienced a decrease in blood pressure along with mucocutaneous erythema. In the most severe case, reintubation after extubation was required due to difficulty in manual ventilation. All patients recovered with anti-allergic therapy. On later investigation, all three patients had a positive skin reaction to sugammadex.ConclusionOur results suggest that physicians using sugammadex should be aware of the possibility of sugammadex-induced anaphylaxis.

Incidence and outcomes of uterine rupture among women with prior caesarean section: who multicountry survey on maternal and newborn health.

Caesarean section (CS) is increasing globally, and women with prior CS are at higher risk of uterine rupture in subsequent pregnancies. However, little is known about the incidence, risk factors, and outcomes of uterine rupture in women with prior CS, especially in developing countries. To investigate this, we conducted a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health, which included data on delivery from 359 facilities in 29 countries. The incidence of uterine rupture among women with at least one prior CS was 0.5% (170/37,366), ranging from 0.2% in high-Human Development Index (HDI) countries to 1.0% in low-HDI countries. Factors significantly associated with uterine rupture included giving birth in medium- or low-HDI countries (adjusted odds ratio [AOR] 2.0 and 3.88, respectively), lower maternal educational level (≤6 years) (AOR 1.71), spontaneous onset of labour (AOR 1.62), and gestational age at birth <37 weeks (AOR 3.52). Women with uterine rupture had significantly higher risk of maternal death (AOR 4.45) and perinatal death (AOR 33.34). Women with prior CS, especially in resource-limited settings, are facing higher risk of uterine rupture and subsequent adverse outcomes. Further studies are needed for prevention/management strategies in these settings.

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.

Objective To 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. Design Secondary analysis of a cross-sectional study. Setting Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health. Population 29,647 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. Methods We 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 Measures Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality. Results Odds 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. Conclusions Elective 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.

Diagnostic Accuracy of Ultrasound Scanning for Prenatal Microcephaly in the context of Zika Virus Infection: A Systematic Review and Meta-analysis

To assess the accuracy of ultrasound measurements of fetal biometric parameters for prenatal diagnosis of microcephaly in the context of Zika virus (ZIKV) infection, we searched bibliographic databases for studies published until March 3rd, 2016. We extracted the numbers of true positives, false positives, true negatives, and false negatives and performed a meta-analysis to estimate group sensitivity and specificity. Predictive values for ZIKV-infected pregnancies were extrapolated from those obtained for pregnancies unrelated to ZIKV. Of 111 eligible full texts, nine studies met our inclusion criteria. Pooled estimates from two studies showed that at 3, 4 and 5 standard deviations (SDs) <mean, sensitivities were 84%, 68% and 58% for head circumference (HC); 76%, 58% and 58% for occipitofrontal diameter (OFD); and 94%, 85% and 59% for biparietal diameter (BPD). Specificities at 3, 4 and 5 SDs below the mean were 70%, 91% and 97% for HC; 84%, 97% and 97% for OFD; and 16%, 46% and 80% for BPD. No study including ZIKV-infected pregnant women was identified. OFD and HC were more consistent in specificity and sensitivity at lower thresholds compared to higher thresholds. Therefore, prenatal ultrasound appears more accurate in detecting the absence of microcephaly than its presence.

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China

BackgroundChina has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China.MethodsA Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios.ResultsHPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD

Assessment and support during early labour for improving birth outcomes

23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60%xa0~xa070% did the HPV2 and screening combination strategy become economically feasible.ConclusionsThe combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Accuracy of ultrasound scanning relative to reference tests for prenatal diagnosis of microcephaly in the context of Zika virus infection: a systematic review of diagnostic test accuracy

BACKGROUNDnThe progress of labour in the early or latent phase is usually slow and may include painful uterine contractions. Women may feel distressed and lose their confidence during this phase. Support and assessment interventions have been assessed in two previous Cochrane Reviews. This review updates and replaces these two reviews, which have become out of date.nnnOBJECTIVESnTo investigate the effectiveness of assessment and support interventions for women during early labour.In order to measure the effectiveness of the interventions, we compared the duration of labour, the rate of obstetrical interventions, and the rate of other maternal or neonatal outcomes.nnnSEARCH METHODSnWe searched the Cochrane Pregnancy and Childbirth Groups Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 October 2016) and reference lists of retrieved studies.nnnSELECTION CRITERIAnRandomised controlled trials of any assessment or support intervention in the latent phase of labour. We planned to include cluster-randomised trials if they were eligible. We did not include quasi-randomised trials.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We resolved any disagreement by discussion or by involving a third assessor. The quality of the evidence was assessed using the GRADE approach.nnnMAIN RESULTSnWe included five trials with a total of 10,421 pregnant women in this review update. The trials were conducted in the UK, Canada and America. The trials compared interventions in early labour versus usual care. We examined three comparisons: early labour assessment versus immediate admission to hospital; home visits by midwives versus usual care (telephone triage); and one-to-one structured midwifery care versus usual care. These trials were at moderate- risk of bias mainly because blinding women and staff to these interventions is not generally feasible. For important outcomes we assessed evidence using GRADE; we downgraded evidence for study design limitations, imprecision, and where we carried out meta-analysis, for inconsistency.One trial with 209 women compared early labour assessment with direct admission to hospital. Duration of labour from the point of hospital admission was reduced for women in the assessment group (mean difference (MD) -5.20 hours, 95% confidence interval (CI) -7.06 to -3.34; 209 women, low-quality evidence). There were no clear differences between groups for the number of women undergoing caesarean section or instrumental vaginal birth (risk ratio (RR) 0.72, 95% CI 0.30 to 1.72, very low quality evidence; and, RR 0.86, 95% CI 0.58 to 1.26, very low quality evidence, respectively). Serious maternal morbidity was not reported. Women in the early assessment group were slightly less likely to have epidural anaesthesia (RR 0.87, 95% CI 0.78 to 0.98, low-quality evidence), and considerably less likely to have oxytocin for labour augmentation (RR 0.57, 95% CI 0.37 to 0.86) and this group also had increased satisfaction with their care compared with women in the immediate admission group (MD 16.00, 95% CI 7.53 to 24.47). No babies were born before admission to hospital and only one infant had a low Apgar score at five minutes after the birth (very low quality evidence). Admission to neonatal special care was not reported.Three studies examined home assessment and midwifery support versus telephone triage. One trial reported the duration of labour; home visits did not appear to have any clear impact compared with usual care (MD 0.29 hours, 95% CI -0.14 to 0.72; 1 trial, 3474 women, low-quality evidence). There was no clear difference for the rate of caesarean section (RR 1.05, 95% CI 0.95 to 1.17; 3 trials, 5170 women; I² = 0%; moderate-quality evidence) or the rate of instrumental vaginal birth (average RR 0.95, 95% CI 0.79 to 1.15; 2 trials, 4933 women; I² = 69%; low-quality evidence). One trial reported birth before arrival at hospital or unplanned home birth; there was no clear difference between the groups (RR 1.33, 95% CI 0.30 to 5.95; 1 trial, 3474 women). No clear differences were identified for serious maternal morbidity (RR 0.93, 95% CI 0.61 to 1.42; 1 trial, 3474 women; low-quality evidence), or use of epidural (average RR 0.95, 95% CI 0.87 to 1.05; 3 trials, 5168 women; I² = 60%; low-quality evidence). There were no clear differences for neonatal admission to special care (average RR 0.84, 95% CI 0.50 to 1.42; 3 trials, 5170 infants; I² = 71%; very low quality evidence), or for Apgar score less than seven at five minutes after birth (RR 1.19, 95% CI 0.71 to 1.99; 3 trials, 5170 infants; I² = 0%; low-quality evidence).One study, with 5002 women, examined one-to-one structured care in early labour versus usual care. Length of labour was not reported. There were no clear differences between groups for the rate of caesarean section (RR 0.93, 95% CI 0.84 to 1.02; 4996 women, high-quality evidence), or for instrumental vaginal birth (RR 0.94, 95% CI 0.82 to 1.08; 4996 women, high-quality evidence). No clear differences between groups were reported for serious maternal morbidity (RR 1.13, 95% CI 0.84 to 1.52; 4996 women, moderate-quality evidence). Use of epidural was similar in the two groups (RR 1.00, 95% CI 0.99 to 1.01; 4996 women, high-quality evidence). For infant outcomes, there were no clear differences between groups (admission to neonatal intensive care unit: RR 0.98, 95% CI 0.80 to 1.21; 4989 infants, high-quality evidence; Apgar score less than seven at five minutes: RR 1.07, 95% CI 0.64 to 1.79; 4989 infants, moderate-quality evidence).nnnAUTHORS CONCLUSIONSnAssessment and support in early labour does not have a clear impact on rate of caesarean section or instrumental vaginal birth, or whether the baby was born before arrival at hospital or in an unplanned home birth. However, evidence suggested that interventions may have an impact on reducing the use of epidural anaesthesia, labour augmentation and on increasing maternal satisfaction with giving birth. Evidence about the effectiveness of early labour assessment versus immediate admission was very limited and more research is needed in this area.

Risk factors of long hospital stay for immunoglobulin A vasculitis: Single-center study

Objective: To assess the accuracy of ultrasound measurements of fetal biometric parameters for prenatal diagnosis of microcephaly in the context of Zika virus (ZIKV) infection. Methods: We searched MEDLINE, EMBASE, CINAHL, CDTA and other bibliographic databases for studies published until 3rd March 2016. We extracted the numbers of true positives, false positives, true negatives and false negatives and performed meta-analysis to estimate group sensitivity and specificity, where possible. Predictive values for ZIKVinfected pregnancies were extrapolated from those obtained for pregnancies unrelated to ZIKV. Results: Out of 111 eligible full texts, nine studies met our inclusion criteria. Pooled estimates from two studies showed that at 3, 4 and 5 standard deviations (SDs) < mean, sensitivities were 84%, 68% and 58% for head circumference (HC); 76%, 58% and 58% for occipito-frontal diameter (OFD); and 94%, 85% and 59% for biparietal diameter (BPD). Specificities at 3, 4 and 5 SDs below the mean were 70%, 91% and 97% for HC; 84%, 97% and 97% for OFD; and 16%, 46% and 80% for BPD. No study including ZIKV-infected pregnant women was identified. Extrapolated positive predictive values for ZIKV-infected pregnancies at 3, 4 and 5 SD < mean were 2.6%, 6.7% and 15.6% for HC; 4.3%, 15.6% and 15.6% for OFD; and 1.0%, 1.4% and 2.8% for BPD, respectively. Negative predictive values at 3, 4 and 5 SDs < mean were over 99% for HC, OFD, and BPD. Five out of seven studies with descriptive data reported high rates of false positives when ultrasound is applied for prenatal diagnosis of microcephaly. Conclusion: Prenatal ultrasound appears more accurate in detecting the absence of microcephaly than its presence.