Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

BACKGROUND: In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post-partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. METHODS: In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6 × 109 colony-forming units) was taken daily by mothers from 14-16 weeks of gestation till 6 months post-partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. RESULTS: Women were randomized to HN001 (N = 212) or placebo (N = 211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD ≥ 10, wheeze or atopic sensitization in the infant by 12 months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19-0.79, P = .009) and SCORAD (HR = 0.61, 95% 0.37-1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF-ß/IgA profiles were unchanged. CONCLUSION: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

Birth attendants as perinatal verbal autopsy respondents in low- and middle-income countries: a viable alternative?

OBJECTIVE: To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed. FINDINGS: For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%. For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent. CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.

Causes of community stillbirths and early neonatal deaths in low-income countries using verbal autopsy: an International, Multicenter Study.

OBJECTIVE: Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries. STUDY DESIGN: This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD). RESULT: There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%). CONCLUSION: Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.

OBJECTIVE: To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. METHODS: The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. RESULTS: There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. CONCLUSION: This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Using verbal autopsy to ascertain perinatal cause of death: are trained non-physicians adequate?

OBJECTIVES: To develop a standardized verbal autopsy (VA) training program and evaluate whether its implementation resulted in comparable knowledge required to classify perinatal cause of death (COD) by physicians and non-physicians. METHODS: Training materials, case studies, and written and mock scenarios for this VA program were developed using conventional VA and ICD-10 guidelines. This program was used to instruct physicians and non-physicians in VA methodology using a train-the-trainer model. Written tests of cognitive and applied knowledge required to classify perinatal COD were administered before and after training to evaluate the effect of the VA training program. RESULTS: Fifty-three physicians and non-physicians (nurse-midwives/nurses and Community Health Workers [CHW]) from Pakistan, Zambia, the Democratic Republic of Congo, and Guatemala were trained. Cognitive and applied knowledge mean scores among all trainees improved significantly (12.8 and 28.8% respectively, P < 0.001). Cognitive and applied knowledge post-training test scores of nurse-midwives/nurses were comparable to those of physicians. CHW (high-school graduates with 15 months or less formal health/nursing training) had the largest improvements in post-training applied knowledge with scores comparable to those of physicians and nurse-midwives/nurses. However, CHW cognitive knowledge post-training scores were significantly lower than those of physicians and nurses. CONCLUSIONS: With appropriate training in VA, cognitive and applied knowledge required to determine perinatal COD is similar for physicians and nurses-midwives/nurses. This suggests that midwives and nurses may play a useful role in determining COD at the community level, which may be a practical way to improve the accuracy of COD data in rural, remote, geographic areas.

A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. OBJECTIVE: To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. METHODS: Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infant's cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. RESULTS: Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. CONCLUSION: We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet.

INTRODUCTION: To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3650 m). METHODS: Prospective observational study of 1121 vaginal deliveries. RESULTS: Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss > or = 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), pre-term delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1000 live births) and 19 early neonatal deaths (17/1000 live births). CONCLUSION: This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes.

Neonatal death after hypoxic ischaemic encephalopathy: does a postmortem add to the final diagnoses?

BACKGROUND: Case review after fatal perinatal asphyxia may have medicolegal implications. Accurate diagnosis of cause of death is therefore essential. OBJECTIVE: To determine consent rate and utility of autopsy after fatal grade III hypoxic ischaemic encephalopathy (HIE) presumed to be secondary to birth asphyxia. DESIGN: A retrospective clinical review from January 1995 to December 2002. SETTING: Regional tertiary referral neonatal unit, Wellington, New Zealand. POPULATION: Inclusion criteria were gestation >/=37 weeks, resuscitation after delivery and clinical course of grade III HIE. Exclusions were a recognised major lethal malformation. METHODS: Review of clinical records including the autopsy report. MAIN OUTCOME MEASURES: Consent for autopsy, change in diagnosis after autopsy. RESULTS: Twenty-three infants died during the time period with a major diagnosis of grade III HIE. Three did not meet inclusion criteria. Of the remaining 20, 11 were female. Median gestation at birth was 40 weeks (range 38-42 weeks) and median birth weight was 3568 g (range 2140-4475 g). In 8/17 of the infants for whom length and head measurements were available, the Ponderal Index suggested intrauterine growth retardation. The 16/20 infants had an autopsy. Four of these were Coroner's cases giving an autopsy rate of 80% with a rate by consent of 60%. In 10 (62.5%) infants, significant new information was added to the clinical diagnoses. CONCLUSIONS: Neonatal HIE is a symptom rather than a final clinical diagnosis. A full autopsy is required to fully explore the reasons for fatal neonatal HIE and may provide information that is important medicolegally.

Presacral neuroenteric fistula in a newborn presenting with an epidural abscess: case report and review of the literature.

We describe a newborn infant (<24 hours of age) who presented with mild swelling on the back and buttocks attributable to a neuroenteric fistula complicated by an epidural parasacral abscess infected with mixed coliforms. Epidural abscesses in infancy are extremely rare, and one has not been observed previously in the newborn period. The infant was surprisingly mildly affected. Prompt intervention led to an excellent outcome. Coliforms may colonize the infant gut in <24 hours, even in the developed world. Unexplained swellings on the backs of infants should lead to a search for underlying malformations and an early surgical review, which is best conducted with a combined pediatric surgical and neurosurgical approach.