Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare ...the effect of delivering early with delaying birth for as long as possible.
548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726.
Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1·1 (0·7–1·8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen.
The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development.
To test the hypothesis that self-reported physical functioning is more influenced by pain than performance-based physical functioning.
163 knee-osteoarthritis patients completed the performance-based ...DynaPort
® KneeTest (DPKT), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and SF-36 (self-report measures of pain and physical functioning) before, 3, 6, and 12 months after knee replacement.
Correlations between (two) self-reported measures of functioning and (two) pain measures were higher (0.57–0.74) than correlations between the performance-based measure of functioning and the two pain measures (0.20 and 0.26). In factor analysis, WOMAC and SF-36 pain and physical functioning subscores loaded on the first factor (eigenvalue 3.2), while DPKT KneeScore2 loaded on the second factor (eigenvalue 0.92). Before surgery, correlations between performance-based and self-reported physical functioning were higher in patients with less pain (0.43) compared to patients with more pain (0.17), for the WOMAC (as expected), but not for the SF-36. After surgery, when the pain had diminished, the correlations between performance-based and self-reported physical functioning were higher, especially for the WOMAC.
Our hypothesis was convincingly supported by the results of the WOMAC, and somewhat less by the results of the SF-36. We consider this as evidence for a lack of content validity of the WOMAC.
Perinatal exposure to Dutch background dioxin levels is rather high. Studies of calamities have shown that dioxins negatively influence the respiratory system. It was hypothesized that perinatal ...exposure to background dioxin levels leads to lung suboptimality, probably through developmental interference. This study aimed to assess lung function in relation to perinatal dioxin exposure. Spirometry was performed in 41 healthy children (aged 7‐12 y, mean 8.2 y) with known perinatal dioxin exposure. The ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC ratio) was determined. A complete medical history was taken. The prenatal exposure ranged from 8.74 to 88.8 (mean 34.6) ng TEQ dioxin kg fat−1, measured in breast milk. The postnatal exposure ranged from 4.34 to 384.51 (mean 75.4) ng TEQ dioxin. Twelve children had to be excluded. A significant decrease in lung function in relation to both prenatal (p= 0.045) and postnatal (p= 0.0002) dioxin exposure was seen in the 29 non‐excluded children. A clinical association between chest congestion and perinatal dioxin exposure was seen.
Conclusion: Perinatal background dioxin exposure may be inversely associated with the FEV1/FVC ratio.
Animal studies have shown that dioxins influence plasma thyroid hormone concentrations. To investigate the effect of chlorinated dioxins and furans on thyroid hormone concentrations in humans, we ...studied 38 healthy breast-fed infants. The study population was divided into two groups according to the dioxin concentrations in milk fat of their mothers. Blood samples were taken at birth and at the ages of 1 and 11 weeks. At birth a tendency to higher total thyroxine ( tT4) concentrations was found in the high exposure group. At the ages of 1 and 11 weeks the increase of mean tT4concentrations and tT4/thyroxine-binding globulin ratios in the high exposure group reached significance as compared to the low exposure group. At birth and 1 week after birth, mean thyrotropin (TSH) concentrations were similar in both groups, but at the age of 11 weeks the mean TSH concentrations were significantly higher in the high exposure group. We postulate that the observed plasma tT4elevation in infants exposed to dioxins before and after birth is the result of an effect on the thyroid hormone regulatory system.
Perinatal exposure to Dutch "background" dioxin levels in 1990 was high, but comparable with that of other industrialized Western European countries. Exposure during the sensitive perinatal period ...may cause permanent disturbances. Therefore, we assessed the health status and various hematologic and immunologic parameters among our longitudinal cohort. A medical history was taken and venipuncture performed in a longitudinal cohort of 27 healthy 8-year-old children who had documented perinatal dioxin exposure. Linear regression revealed a decrease in allergy in relation to prenatal (p = 0.02) and postnatal (p = 0.03) dioxin exposure. Increases in CD4+T-helper cells (p = 0.006) and in CD45 RA+cells (p = 0.02) were seen in relation to postnatal exposure. A persistently decreased platelet count (p = 0.04) and increased thrombopoietin concentration (p = 0.03) were seen in relation to postnatal exposure. This follow-up has shown a decrease in allergy, persistently decreased thrombocytes, increased thrombopoietin, and increased CD4+T-helper and increased CD45 RA+cell counts. This study provides indications of effects at the stem cell level of perinatal dioxin exposure, persisting until minimally 8 years after birth.
Objectives To compare the effect of delivering early to pre‐empt terminal hypoxaemia with delaying for as long as possible to increase maturity.
Design A randomised controlled trial.
Setting 69 ...hospitals in 13 European countries.
Participants Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated.
Methods The interventions were ‘immediate delivery’ or ‘delay until the obstetrician is no longer uncertain’. The data monitoring and analysis were Bayesian.
Main outcome measures ‘Survival to hospital discharge’ and ‘developmental quotient at two years of age’, this latter to be reported later.
Results Of 548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies). The median time‐to‐delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group. Total deaths prior to discharge were 29 (10%) in the immediate group versus 27 (9%) in the delay group (odds ratio 1.1, 95% CI 0.61–1.8). Total caesarean sections were 249 (91%) in the immediate group versus 217 (79%) in the delay group: (OR 2.7; 95% CI 1.6–4.5). These odds ratios were similar for those randomised at gestational ages above or below 30 weeks.
Interpretation The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to randomise at about the correct equivocal threshold between delivery and delay. However, there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong.
Prenatal and lactational exposure to Dutch “background” dioxin levels may cause health effects spanning many years. In addition, perinatal studies have shown a relationship between dioxin exposure ...and thyroid disturbance. To assess the later health effects of prenatal and lactational dioxin exposure on liver function we measured plasma ALAT and ASAT levels amongst our longitudinal cohort, as was done perinatally and at 2½ years. The children underwent a caffeine loading test to determine CYP1A2 activity. To assess the later effects on thyroid function we measured plasma TSH and FT4.
A longitudinal cohort of 37 healthy children (age 7–12, mean 8.2 years), with documented prenatal and lactational dioxin exposure, ingested 3
mg caffeine/kg BW 6
h prior to blood withdrawal. Paraxanthine/caffeine molar ratio, ALAT, ASAT, TSH and FT4 were determined in venous blood.
Linear regression of ASAT and ALAT revealed no relation with prenatal and lactational dioxin exposure. No correlation was found between the paraxanthine/caffeine molar ratio and prenatal and lactational dioxin exposure. Linear regression of TSH and FT4 revealed no relation with prenatal and lactational dioxin exposure.
This follow-up has shown a normalisation of previously abnormal ALAT and ASAT levels, indicating a transient effect. CYP1A2 activity, measured by means of a caffeine-loading test, revealed no correlation with the prenatal and lactational exposures. A normalisation of previously abnormal thyroid hormone homeostasis was seen, also possibly indicating a transient effect. This study provides new data on long-term follow-up after perinatal dioxin exposure to background levels of dioxins.
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