SummaryOne hundred and one pregnant women with hypertensive disorders were prospectively studied with doppler ultrasound flow velocity waveforms of the umbilical artery. Results were withheld from the obstetricians so that the test did not influence obstetric management. It was found that the resistance index of the umbilical artery was higher in patients with proteinuric pregnancy induced hypertension and in patients with chronic hypertension than in patients with non-proteinuric pregnancy induced hypertension. Patients with an abnormal resistance index were more likely to be delivered prematurely, have small for dates babies, have fulminating hypertension and have an abnormal antepartum cardiotocogram. Thirteen patients had a pathological antenatal cardiotocogram and they all had an abnormal umbilical artery flow velocity wave form when the cardiotocogram was normal.

Background Since the global financial crisis, UK NHS spending has reduced considerably, Respiratory care is a large cost driver for Betsi Cadwaladr University Health Board, the largest health board in Wales. Under the remit of 'prudent healthcare' championed by the Welsh Health Minister, a Programme Budgeting Marginal Analysis (PBMA) of the North Wales respiratory care pathway was conducted.Methods A PBMA panel of directors of medicines management, therapies finance, planning, public health and healthcare professionals used electronic voting to establish criteria for decision-making and vote on candidate interventions in which to disinvest and invest.Results A sum of 86.9 pound million was spent on respiratory care in 2012-13. Following extensive discussion of 13 proposed candidate interventions facilitated by a chairperson, 4 candidates received recommendations to disinvest, 7 to invest and 2 to maintain current activity. Marginal analysis prioritized mucolytics and high antibiotic prescribing as areas for disinvestment, and medicines waste management and pulmonary rehabilitation for investment.Conclusions This exercise demonstrates the potential for health boards to use evidence-based approaches to reach potentially controversial disinvestment and investment decisions. Initial progress has begun with communication from the Medical Director in relation to the disinvestment in mucolytics prescribing and possible redirection of funding options being explored.

Evaluating the wood density of standing trees quickly, cheaply and reliably with a minimum of damage is clearly of benefit to wood producers. In this study an IML-Resi F300S field tool, which is a constant-feed drill that measures resistance, was compared with the high-resolution SiviScan2 X-ray and image-analysis instrument for assessing wood density of Eucalyptus globulus subsp. pseudoglobulus. The IML-Resi successfully predicted average wood density but was less reliable for assessing changes in density within a single stem.

In Brief OBJECTIVE: To examine changes in perinatal mortality and birth weight of babies born to mothers with pregestational type 1 diabetes over 40 years in a single teaching hospital clinic. METHODS: This was a retrospective survey of cases from the combined diabetes and obstetrics antenatal clinic at the Royal Infirmary of Edinburgh and Simpson Memorial Maternity Pavilion, Edinburgh, Scotland. Birth weight, standardized birth weight, and perinatal mortality were obtained from 643 singleton babies born after 28 weeks of gestation to mothers with pregestational type 1 diabetes between 1960 and 1999. RESULTS: There was a dramatic improvement in perinatal mortality rate, falling from 225 (per 1,000 total births after 28 weeks of gestation) in the 1960s to 102 in the 1970s, 21 in the 1980s, and 10 in the 1990s (P < .001 for effect of birth year). In contrast, standardized birth weight (adjusted for sex, gestational age, and parity), which was significantly higher than the background population (+1.41 standard deviations above the population norm, P < .001) showed no significant change over time. CONCLUSION: Changes in diabetic management and obstetric practice over the 40 years of our survey have resulted in enormous improvements in the outlook for offspring of mothers with diabetes. Somewhat surprisingly this has not been associated with a reduction in overgrowth of the fetus. LEVEL OF EVIDENCE: II-2 Perinatal mortality decreased in offspring of women with type 1 diabetes, while average birth weight remained virtually unchanged.

objective  Maternal diabetes is associated with excess foetal growth. We have assessed the influence of maternal diabetes on hormones associated with foetal growth and the relationship of these hormones to birthweight.

During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross the placenta. It is proposed that insulin antibodies (IA) allow transfer of insulin across the placenta, contributing to fetal hyperinsulinemia and macrosomia.We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with type 1 diabetes (ODM, n=138) and control mothers ( control, n=47) and further assessed cross-sectional relationships of antibody titers to birth weight and fetal insulin.In ODM, antibodies were frequently present in cord blood; 124 ODM (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61 (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies were absent, whereas seven controls (15%) were positive for IA at low titers (P<0.0001 ODM vs. controls for all).ODM with IA ( IA positive) or without IA ( IA negative) had similar birth weights (mean +/- SD: IA positive, 3.8 +/- 0.7 kg; IA negative, 4.0 +/- 0.6 kg; P=0.31) and cord insulin concentrations (IA positive: median, 112 pmol/liter; interquartile range, 62-219 pmol/liter; IA negative: median, 114 pmol/liter; interquartile range, 59-194 pmol/liter; P=0.96). Similarly, the presence of GADA and/or IA-2 autoantibodies (n=103) was not associated with differences in birth weight or insulin concentrations. Antibody titers were not associated with birth weight or insulin as continuous variables in either controls or ODM.Islet autoantibodies and IA are a common finding in cord blood of ODM, but we found no evidence that they influence offspring insulin concentrations or weight at birth.

OBJECTIVE:In adults, adiponectin is reduced in association with excess adiposity, type 2 diabetes, and hyperinsulinemia. We assessed whether adiponectin was 1) present in the fetal circulation, 2) altered in the fetal circulation in the presence of maternal diabetes, and 3) had relations to fetal cord blood insulin or adiposity.RESEARCH DESIGN AND METHODS:We assessed adiponectin in cord blood in a large cohort of singleton offspring of diabetic mothers (ODM; n = 134) and control mothers (n = 45).RESULTS:Adiponectin was present in cord blood and, in ODM, was higher in those delivered at later gestational ages (Spearman r = 0.18, P = 0.03). Adiponectin was slightly lower in ODM than control subjects (ODM 19.7 +/- 6.1 vs. control 21.8 +/- 5.3 micro g/ml; P = 0.04), although this difference could potentially reflect different gestational ages in the two groups (ODM 37.6 +/- 1.5 and control 40.1 +/- 1.1 weeks). In contrast to adults, adiponectin levels in the fetus were unrelated to the degree of adiposity, blood insulin, or leptin in either control subjects or ODM.CONCLUSIONS:Adiponectin is present in cord blood but does not show expected physiological relations with adiposity as observed in adults.

Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.

Maternal diabetes during pregnancy is associated with excess fetal growth and increased fetal insulin production. We hypothesized that insulin propeptides (proinsulin and 32-33 split proinsulin) might be more robust indicators of chronic fetal overproduction of insulin. We examined insulin-like molecules in cord blood (ILM) (insulin, proinsulin, and 32-33 split proinsulin) in relation to birth weight, maternal glycemia, and cord glucose in 140 offspring of mothers with type 1 diabetes (ODM) and 49 offspring of mothers who did not have diabetes (CONTROL) as well as degradation of ILM in response to sampling conditions at birth. Insulin propeptides were abundant in cord blood, comprising 50% of ILM in CONTROL and 36% in ODM (P < 0.0001) and more resistant to degradation than insulin (P < 0.05). Concentrations of all three ILM were highly intercorrelated with median values 2- to 5-fold higher in ODM than CONTROL [e.g. median (range): insulin ODM 110 (60-217) pmol/liter; CONTROL 22 (15-37) pmol/liter; P < 0.0001]. In ODM, 32-33 split proinsulin and proinsulin were more closely related to birth weight (Spearman r for ILM: r(32-33 split)= 0.54; r(PROINSULIN): r = 0.54; r(INSULIN) = 0.40: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) and fetal leptin (r(32-33 split)= 0.55; r(PROINSULIN); r = 0.54; r(INSULIN) = 0.22: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) than insulin). By contrast, insulin was more closely related to cord glucose (r(32-33 split) = 0.15; r(PROINSULIN): r = 0.10; r(INSULIN) = 0.42: r(INSULIN) > r(32-33 split) and r(PROINSULIN)P < 0.05). In CONTROL, 32-33 split proinsulin was also more closely related to fetal leptin r(32-33 split)= 0.61; r(PROINSULIN): r = 0.29; r(INSULIN) = 0.33: r(32-33 split) > r(INSULIN)P < 0.05). In ODM, 32-33 split proinsulin and proinsulin have closer relationships to fetal growth and leptin concentrations at birth than insulin. Measurement of insulin propeptides may be advantageous in assessment of the influence of maternal hyperglycemia on the newborn.

ObjectiveTo describe changes over a 15-year period in characteristics and management of HIV-infected pregnant women in Europe. DesignProspective study. MethodsAnalysis of prospective data on 2876 pregnant HIV-infected women and their 3076 infants. Factors examined included maternal socio-demographic, immunological and virological characteristics, antiretroviral therapy and pregnancy outcome. ResultsAmong women enrolled, the proportion with heterosexual acquisition of infection has increased significantly from 59% (201/342) in 1985–1987 to 69% (327/471) after 1997 while the proportion acquiring HIV through injecting drug use has declined. Overall median CD4 cell count was 440 × 106/l and 41% of women had undetectable viral load at delivery. In 1995 28% (72/256) of mother–child pairs received the full 076 regimen to reduce risk of vertical transmission, rising significantly to 89% (116/130) by 1999. Use of triple therapy started in pregnancy has increased significantly from < 1% (1/153) in 1997 to 44% (47/107) in 1999. Exposure to antiretroviral therapy was not associated with prevalence or pattern of congenital abnormalities (P = 0.88) but was associated with reversible anaemia in the infant (P < 0.002). The elective cesarean section rate has increased from 10% in 1992 to 71% in 1999/2000. The vertical transmission rate declined from 15.5% by 1994 to 2.6% after 1998. In multivariate analysis, adjusting for maternal CD4 cell count, risk of vertical transmission was reduced by 66% (95% confidence interval, 37–82%) with the full 076 regimen and by 60% (95% confidence interval, 33–73%) with elective cesarean section delivery. ConclusionsChanges in treatment of adult HIV disease have affected the management of infected pregnant women. Despite therapeutic and surgical interventions, vertical transmission still occurs.

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV.Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis.Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded.Results: The primary analysis included 4721 deliveries with duration of ruptured membranes less than or equal to 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01).Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. (C) 2001 Lippincott Williams & Wilkins.

ObjectiveTo assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy. DesignProspective study. MethodsData on 3920 mother–child pairs were examined (3015 mother–child pairs from the European Collaborative Study and 905 from the Swiss Mother + Child HIV Cohort Study). Factors examined included gestational age, antiretroviral therapy during pregnancy, maternal CD4 count, viral load, illicit drug use (IDU) and mode of delivery. Deliveries at less than 37 weeks were defined as premature. ResultsThe prematurity rate was 17% and median gestational age 39 weeks. Twenty-three per cent (896 of 3920) of women received antiretroviral therapy during pregnancy: 64% (573 of 896) zidovudine monotherapy, 24% (215) combination therapy without protease inhibitors (PI) and 12% (108) combination therapy with PI. In multivariate analysis, adjusted for maternal CD4 count and IDU, odds ratio (OR) of prematurity was 2.60 [95% confidence interval (CI), 1.43–4.75] and 1.82 (95% CI, 1.13–2.92) for infants exposed to combination therapy with and without a PI, respectively, compared to no treatment. Exposure to monotherapy was not associated with prematurity, but severe immunosuppression and IDU in pregnancy were. Women on combination therapy from before pregnancy were twice as likely to deliver prematurely as those starting therapy in the third trimester (OR, 2.17; 95% CI, 1.03–4.58). ConclusionsPregnancy issues should be discussed when making decisions about initiation of combination antiretroviral therapy for HIV-infected women. Elective caesarean section to reduce vertical transmission at 36 weeks rather than 38 weeks may be advisable in women on combination therapy with PI.

OBJECTIVE:To identify factors independently affecting fetal weight in women with type I diabetes. DESIGN:Prospectively recorded data in consecutive women with type I diabetes, between 1975-1992. SETTING:Simpson Memorial Maternity Hospital, Edinburgh. Population Three hundred and two pregnancies with type I diabetes identified before pregnancy, with antenatal care and delivery in the Simpson Memorial Maternity Hospital, a singleton pregnancy, and the same diabetic physician. METHODS:Normal ranges for birthweight were established for the total hospital population. All cases and the total population had pregnancy dating by ultrasound. The relation between standardised birthweight and explanatory variables was investigated using correlation analysis, t tests and chi2 tests as appropriate, and subsequently using multiple linear regression. RESULTS:Standardised birthweight in cases, compared with the reference population, showed a unimodal, approximately normal distribution, markedly shifted to the right (mean + 1.26 SD). The most predictive variable was glycated haemoglobin concentration at 27-33 weeks, which explained 6.3% of the birthweight variance, while smoking explained 2.7% and maternal weight 2.0%. There was a trend towards a negative relationship with glycated haemoglobin concentration at 6-12 weeks. Smoking and glycated haemoglobin concentration were strongly intercorrelated. CONCLUSIONS:Most of the variance in standardised birthweight remains unexplained, but glycated haemoglobin concentration at 27-33 weeks is the most powerful explanatory variable. Possible reasons why there is not a stronger relationship between markers of maternal glycaemia and birthweight are discussed.

Objective: Prophylactic zidovudine during pregnancy and labour reduces maternal viral load and, with neonatal therapy, has been shown to reduce vertical transmission. However, zidovudine may have additional effects. Advanced HIV disease is associated with premature delivery, which in turn results in increased vertical transmission. Data from the European Collaborative Study (ECS) were analysed to investigate whether zidovudine could be associated with decreased prematurity risk and/or with a reduced frequency of low birthweight.Methods: HIV-infected pregnant women enrolled in the ECS were followed prospectively according to a standard protocol. Gestational age was assessed by ultrasound, prematurity was defined as delivery before 37 weeks and the cut-off for low birthweight was 2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on the risk of premature or low birthweight delivery.Results: In 2299 mothers, zidovudine taken to reduce the risk of vertical transmission decreased the odds of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53-1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39-0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR values. A multivariate analysis suggested that prophylactic zidovudine and prematurity were independently associated with risk of transmission.Conclusion: Our findings suggest an additional health benefit of zidovudine. Even ii most vertical transmission occurs around the time of delivery, therapy earlier in pregnancy could have an indirect effect on transmission rates through delaying delivery. This hypothesis needs to be confirmed or refuted by more appropriate studies.

Before any new antenatal screening test is introduced, the opinions of pregnant women should be considered. This is particularly relevant with HIV testing. This qualitative study reports the views of 29 women attending an antenatal clinic in a large maternity hospital in Scotland where a trial of different ways of offering HIV testing on a universal, voluntary basis occurred. Women were in favour of a test offer, although they did not necessarily wish to accept testing for themselves. Generally they were more worried about having an unhealthy baby. There was a commonly held view that routine testing would cause less anxiety because it would eliminate the stigma of saying yes to testing. A move towards the HIV test being recommended to pregnant women as opposed to merely offered is likely to be acceptable, would probably increase uptake rates and should therefore be assessed.

Papers pp 16501656The benefits of testing pregnant women for HIV are increasingly assured, particularly with regard to reducing vertical transmission.1 Yet uptake of antenatal HIV testing in Britain remains low.2 Our previous study examined an opt-in approach (women had to make an active choice to be tested).3 Some women were uncomfortable with this, feeling that it indicated high risk behaviour. We therefore assessed an approach based on similar requirements for information and consent but with a change in emphasis, in that testing was routine unless the woman declined.The testing programme was conducted during February to April 1998. Before their booking appointment, all women were sent a leaflet about blood tests to be conducted, including HIV testing. At the antenatal clinic they were offered an HIV test by midwives who had been trained to use a printed discussion protocol that emphasised the benefits and presented the test as routine, making it clear that the woman could decline. As with the other blood …