Maternal serum insulin-like growth factor binding protein-2 and -3 and fetal growth.

This was a prospective observational study of maternal insulin-like growth factor binding protein-2 and -3 and fetal growth in 141 pregnant women after 24 weeks gestation who were scanned and venesected fortnightly. Cases (birthweight <5th centile) were sub-divided into those with growth restriction due to placental dysfunction (n = 25) and normal small (n = 27) and there were 89 normally grown controls. Maternal binding protein-3 was measured by radioimmunoassay and the overall pattern of the binding proteins and their proteolytic modifications were assessed by Western ligand blotting and immunoblotting followed by densitometric analysis. In controls, there was no correlation between binding protein-3 and birthweight, and binding protein-3 was elevated in the normal small but not the placental dysfunction group. Complete proteolysis of the 40 kDa doublet of binding protein-3 was observed in all pregnancies. Maternal serum binding protein-2 concentrations were unchanged in normal pregnancy compared to non-pregnant controls but elevated in the growth-restricted group and in all pregnancies binding protein-2 was predominantly present as a 14 kDa proteolysed fragment. These results suggest that compensatory changes in binding protein-2 and -3 or their proteolysis do not increase bioavailability and so do not confound the low maternal insulin-like growth factor-I in growth restricted pregnancies.     

Maternal social support predicts birth weight and fetal growth in human pregnancy

OBJECTIVE: Low birth weight is a primary cause of infant mortality and morbidity. Results of previous studies suggest that social support may be related to higher birth weight through fetal growth processes, although the findings have been inconsistent. The purpose of this investigation was to test a model of the association between a latent prenatal social support factor and fetal growth while taking into account relations between sociodemographic and obstetric risk factors and birth weight. METHOD: A prospective study was conducted among 247 women with a singleton, intrauterine pregnancy receiving care in two university-affiliated prenatal clinics. Measures of support included support from family, support from the baby's father, and general functional support. Sociodemographic characteristics were also assessed. Birth outcome and obstetric risk information were abstracted from patients' medical charts after delivery. RESULTS: Structural equation modeling analyses showed that a latent social support factor significantly predicted fetal growth (birth weight adjusted for length of gestation) with infant sex, obstetric risk, and ethnicity in the model. Marital status and education were indirectly related to fetal growth through social support. The final model with social support and other variables accounted for 31% of the variance in fetal growth. CONCLUSIONS: These findings suggest that prenatal social support is associated with infant birth weight through processes involving fetal growth rather than those involving timing of delivery. Biological and behavioral factors may contribute to the association between support and fetal growth, although these mechanisms need to be further explored. These results pave the way for additional research on fetal growth mechanisms and provide a basis for support intervention research.     

Respiratory changes and structure of sleep in young high-altitude dwellers in the Andes of Peru

Summary Sleep organisation in eight young [mean (SD); 20·9 (2·6) years] Peruvian high-altitude residents was studied in a laboratory in Cerro de Pasco at 4300 m. Electroencephalograms, electromyograms, electro-oculograms, electrocardiograms, respiratory movements and arterial oxyen saturation were recorded on an 8-channel Medilog recorder and analysed later in England. Haematocrits ranged from 48% to 64% [57.9 (5.6)%]. The amount of slow wave rapid eye movement (REM) sleep was similar to that reported in young lowlanders sleeping at sea level but very different to the disturbed sleep in visitors sleeping at high altitude. All the Peruvians showed episodes of periodic breathing and respiratory apnoeas [29 (15) night^–1] resulting in marked arterial oxygen desaturation [81 (4.5)%; changes of 6 (2.5)%]. These events occurred either during stage 2 or REM sleep and were more frequent in those with lower haematocrits. The amount of wakefulness during the night was 2–3 times greater than would be expected in an age-matched lowland population at sea level. The awakenings were strongly associated with apnoeas (P<0.02) but were negatively correlated with the haematocrit, although this was only significant for seven of the subjects (P<0.05).     

Diffusive resistance to O2 transport in muscle

Although it has been generally well-accepted since the work of August Krogh at the start of the 20th century that O2 travels between muscle microvascular red cells and muscle mitochondria by diffusion, the importance of this process to maximal O2 flux remains in question. This review presents data that suggest maximal rates of diffusion of O2 in muscle are limited by both the amount of capillary structure and the haemoglobin concentration in the blood. On the other hand, diffusional conductance appears unrelated to muscle fibre size and thus to distance. Functional data further suggest that the limited rate of diffusion acts to constrain O2 unloading from muscle capillaries and thus also maximal Vo2, at least in the trained state. In fact, the calculated sensitivity of VO2max to muscle diffusional conductance is about as great as that for muscle blood flow. While additional impairment of O2 unloading from perfusion/metabolism heterogeneity cannot yet be excluded (for lack of methodology), it seems evident that the process of O2 transport between the muscle microvasculature and the mitochondria is subject to significant limits, even in health, that have substantial effects on maximal Vo2.     

Maternal and fetal outcome of gestational diabetes mellitus in Mulago Hospital, Uganda

Objective

To determine the maternal and foetal outcomes in mothers with gestational diabetes mellitus attending antenatal clinics in Mulago Hospital Kampala Uganda.

Design

This was a cohort study.

Setting

Mulago Hospital antenatal clinics.

Participants

Ninety mothers with gestational ages between 24–32 weeks were recruited from April to September 2001.They were followed up to the time of delivery. The WHO criterion for the diagnosis of gestational diabetes was used. Thirty mothers with a 2 hrs post prandial capillary blood sugar more than 140 mg/dl were the exposed group and 60 mothers with less than 140 mg/dl were the unexposed group. Blood sugar was measured using a one touch glucometer.

Outcome variables

Socio demographic characteristics, maternal complications, mode of delivery and the foetal outcomes.

Results

The mean age of mothers in both groups was similar: 28.6 years vs 27.5 years. Both groups had similar body mass index more than 26. The mothers with gestational diabetes mellitus (GDM) were four times more likely to have hypertensive disease(p=0.04) and nine times more likely to have vaginal candidiasis(p=0.002).The modes of delivery were similar in both groups but genital injuries were more common among mothers with GDM. The indications of Caesarian section in mothers with GDM were two times more likely to be due to big babies and obstructed labour. The babies for mothers with GDM were more likely to be macrocosmic, still born, and have shoulder dystocia than those of normal mothers.

Conclusion

Gestational diabetes mellitus exists in Uganda and is associated with adverse maternal and foetal outcomes. There is need to routinely screen mothers for gestational diabetes in this environment.     

Maternal Schistosomiasis japonica is associated with maternal, placental, and fetal inflammation

Schistosomes infect ～40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1β, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.     

Tracing shigatoxigenic Escherichia coli O103, O145, and O174 infections from farm residents to cattle

Severe diarrheal infections caused by Shigatoxigenic Escherichia coli O103:H2:stx(1):eae-epsilon:ehx, O145:H28:stx(1):eae-gamma:ehx (two cases in a family), and O174:H21:stx(2c) in farm residents were traced to cattle. Molecular methods were applied to the isolation and characterization of the strains. The causative strains were also isolated from cattle samples 1 or 4 months later.     

Acid-base balance and O2 transport at high altitude

Ear lobe blood pH_a, P_aCO ₂, P_aO ₂, and O₂ saturation (S_aO₂) were measured in healthy Caucasians and Sherpas at 3400 m (Namche Bazaar, Nepal, n=4/5), 5050 m (Pyramid Laboratory, Lobuche, Nepal, n=20/5) and 6450 m (Camp II of Mt Everest, n=11/7). In the investigated altitude range, pH_a increased progressively with altitude from 7.463±0.005 (mean±SE) to 7.496±0.006 in Caucasians whereas it remained essentially constant (7.45–7.46) in Sherpas. At all altitudes, P_aCO ₂ was higher in Sherpas than in Caucasians (P<0.02). By contrast, P_aO ₂ and S_aO₂ were the same in Caucasians and Sherpas at all investigated altitudes. Moreover, in Caucasians sojourning for 3 weeks at 5050 m, P_aCO ₂ kept decreasing whereas pH_a, P_aO ₂ and S_aO₂ remained constant. These data suggest that: (1) respiratory alkalosis was a common finding both in Caucasians and Sherpas; (2) at 6450 m, Sherpas were less alkalotic due to higher P_aCO ₂ than Caucasians, possibly a consequence of a blunted ventilatory response; (3) at 6450 m, S_aO₂ and P_aO ₂ were the same in Caucasians and Sherpas despite different P_aCO ₂ values. The latter finding could be the consequence of one or more of the following adjustments in Sherpas: (1), an increased efficiency of alveolar O₂ transfer, i.e. smaller alveolar-arterial O₂ gradient; (2) a decreased (arterial – mixed venous) O₂ difference, possibly due to increased cardiac output; (3) a reduced increase of the [2,3-DPG]/[Hb] ratio; but not (4) an elevated gas exchange ratio (R). It is concluded that both physiological and biochemical variables contribute to optimize the O₂ transport at altitude. Apparently a more efficient adaptation to hypoxia allows Sherpas to limit alkalosis through a lower ventilatory drive and to maintain S_aO₂ at the same P_aO ₂ by decreasing the [2,3-DPG]/[Hb] ratio.     

Maternal and fetal insulin-like growth factors and their binding proteins in the second and third trimesters of human pregnancy

The insulin-like growth factors (IGFs) are mitogenic polypeptides which circulate bound to a series of at least six binding proteins (IGFBPs). An increasing body of evidence supports a major role for the IGF in the control of human fetal growth although normal values in the human fetal circulation have not been established. In order to provide an accurate reflection of fetal IGFs and IGFBPs in utero, we have sampled fetal blood direct from the umbilical cord at 18-38 weeks of gestation using the technique of cordocentesis. We have measured IGF-I, IGF-II and IGFBP 1-3 in 91 fetuses in order to establish concentrations for these parameters in the second and third trimesters of human pregnancy.      

Psoriasis vulgaris,fetal growth,and genomic imprinting

We report on 2 independent lines of evidence suggesting genomic imprinting of a major gene for psoriasis vulgaris. First, the birth weight of children from psoriatics is influenced by the sex of the psoriatic parent. Children from fathers with psoriasis are considerably (270 g) heavier than children from mothers with psoriasis (P<0.004). Second, the disease manifestation (penetrance) depends in part on the sex of the psoriatic parent. Offspring from fathers with psoriasis and male “gene carriers” are significantly (P<0.015 and P<0.007) more often affected than offspring from mothers with psoriasis and female “gene carriers.” Of 91 grandchildren with psoriasis 59 (65%) have an affected grandfather and 32 (35%) a psoriatic grandmother. This deviation from the expected distribution is significant (P<0.04). Genomic imprinting is considered a special case of epigenetic modification. We propose that epigenetic modification. of a major predisposing gene in somatic tissues could cause differences in disease activity of psoriasis and could account for the often unpredictable clinical course the disease takes.     

Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport

The discovery of the S-shaped O2 equilibrium curve and the Bohr effect in 1904 stimulated a fertile and continued research into respiratory functions of blood and allosteric mechanisms in haemoglobin (Hb). The Bohr effect (influence of pH/CO2 on Hb O2 affinity) and the reciprocal Haldane effect (influence of HbO2 saturation on H+/CO2 binding) originate in the Hb oxy-deoxy conformational change and allosteric interactions between O2 and H+/CO2 binding sites. In steady state, H+ is passively distributed across the vertebrate red blood cell (RBC) membrane, and intracellular pH (pHi) changes are related to changes in extracellular pH, Hb-O2 saturation and RBC organic phosphate content. As the Hb molecule shifts between the oxy and deoxy conformation in arterial-venous gas transport, it delivers O2 and takes up CO2 and H+ in tissue capillaries (elegantly aided by the Bohr effect). Concomitantly, the RBC may sense local O2 demand via the degree of Hb deoxygenation and release vasodilatory agents to match local blood flow with requirements. Three recent hypotheses suggest (1) release of NO from S-nitroso-Hb upon deoxygenation, (2) reduction of nitrite to vasoactive NO by deoxy haems, and (3) release of ATP. Inside RBCs, carbonic anhydrase (CA) provides fast hydration of metabolic CO2 and ensures that the Bohr shift occurs during capillary transit. The formed H+ is bound to Hb (Haldane effect) while HCO3- is shifted to plasma via the anion exchanger (AE1). The magnitude of the oxylabile H+ binding shows characteristic differences among vertebrates. Alternative strategies for CO2 transport include direct HCO3- binding to deoxyHb in crocodilians, and high intracellular free [HCO3-] (due to high pHi) in lampreys. At the RBC membrane, CA, AE1 and other proteins may associate into what appears to be an integrated gas exchange metabolon. Oxygenation-linked binding of Hb to the membrane may regulate glycolysis in mammals and perhaps also oxygen-sensitive ion transport involved in RBC volume and pHi regulation. Blood O2 transport shows several adaptive changes during exposure to environmental hypoxia. The Bohr effect is involved via the respiratory alkalosis induced by hyperventilation, and also via the pHi change that results from modulation of RBC organic phosphate content. In teleost fish, beta-adrenergic activation of Na+/H+ exchange rapidly elevates pHi and O2 affinity, particularly under low O2 conditions.