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The fetal demand for FFA increases as gestation proceeds, and LPL represents one potential mechanism for increasing placental lipid transport. We examined LPL activity and protein expression in first trimester and term human placenta. The LPL activity was 3-fold higher in term (n = 7; P < 0.05) compared with first trimester (n = 6) placentas. The LPL expression appeared lower in microvillous membrane from first trimester (n = 2) compared with term (n = 2) placentas. We incubated isolated placental villous fragments with a variety of effectors [GW 1929, estradiol, insulin, cortisol, epinephrine, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-α] for 1, 3, and 24 h to investigate potential regulatory mechanisms. Decreased LPL activity was observed after 24 h of incubation with estradiol (1 μg/ml), insulin, cortisol, and IGF-1 (n = 12; P < 0.05). We observed an increase in LPL activity after 3 h of incubation with estradiol (20 ng/ml) or hyperglycemic medium plus insulin (n = 7; P < 0.05). To conclude, we suggest that the gestational increase in placental LPL activity represents an important mechanism to enhance placental FFA transport in late pregnancy. Hormonal regulation of placental LPL activity by insulin, cortisol, IGF-1, and estradiol may be involved in gestational changes and in alterations in LPL activity in pregnancies complicated by altered fetal growth. more...

Background: Child Health Services plays an important role in identifying at-risk children and intervening early to break negative trends in child health. Sociodemographic risk factors can impact the workload of Child Health Services and affect the possibilities of providing the national child healthcare programme., Aims: This study aims to present the sociodemographic characteristics of families who are registered within the Child Health Services, as defined by the Child adjusted Care Need Index., Methods: By collecting personal identification numbers from children six years or younger registered at a child healthcare centre, and combining this with their caregiver's sociodemographic background, this study was able to create a sociodemographic index for each child healthcare centre in Sweden., Results: The study included 687,543 children and 1,335,540 caregivers from 981 child healthcare centres in Sweden. Approximately 21% of all children in the study population had a caregiver born in Southern or Eastern Europe outside the European Union, or in Africa, Asia, or South America, 7% had single parents, 17% had at least one unemployed caregiver, and 9% had at least one caregiver who had not completed high school. The average input values and the average index values varied widely both between and within the regions., Conclusions: This study displays a large variation in sociodemographics for child healthcare centres both within and between regions. Since several regions and national agencies in Sweden use the Child adjusted Care Need Index, it is necessary to keep the dispersion in mind., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare. more...

Background: Swedish child health services (CHS) is a free-of-charge healthcare system that reaches almost all children under the age of 6. The aim for the CHS is to improve children's physical, psychological and social health by promoting health and development, preventing illness and detecting emerging problems early in the child's life. The services are defined in a national programme divided into three parts: universal interventions, targeted interventions and indicated interventions.The Swedish Child Health Services Register (BHVQ) is a national Quality Register developed in 2013. The register extracts data from the child's health record and automatically presents current data in real time. At present, the register includes 21 variables., Aim: We aim to describe data available in the BHVQ and the completeness of data in BHVQ across variables., Methods: Child-specific data were exported from the register, and data for children born in the regions were retrieved from Statistics Sweden to calculate coverage., Results: The register includes over 110 000 children born between 2011 and 2022 from 221 child healthcare centres in eight of Sweden's 21 regions. In seven of the eight regions, 100% of centres report data.The completeness of data differs between participating regions and birth cohorts. The average coverage for children born in 2021 is 71%., Conclusions: The BHVQ is a valuable resource for evaluating Child Health Services nationally, with high coverage for the youngest children. As a result of continuous improvement of the services, the possibility to follow the development of children's health in Sweden is possible through the register. When fully expanded, the register will be a natural and essential part of developing preventive services, improving healthcare for children below 6 years of age and a tool for developing evidence-based child health interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Background: Current evidence suggests a combined treatment of postpartum weight loss of diet and exercise. However, to our knowledge, neither their separate and interactive effects nor long-term outcomes have been evaluated., Objective: We evaluated whether a 12-wk dietary behavior modification (D) treatment to decrease energy intake, physical exercise behavior modification (E) treatment to implement moderate aerobic exercise, or combined dietary and physical exercise behavior modification (DE) treatment compared with control (usual care) (C) reduces body weight in lactating women measured at the end of treatment and at a 1-y follow-up 9 mo after treatment termination., Design: At 10-14 wk postpartum, 68 lactating Swedish women with a prepregnancy BMI (in kg/m²) of 25-35 were randomly assigned to D, E, DE, or C groups. Measurements were made at baseline, after the intervention, and again at a 1-y follow-up 9 mo later. A 2 × 2 factorial approach was used to analyze main and interaction effects of treatments., Results: Weight changes after the intervention and 1-y follow-up were -8.3 ± 4.2 and -10.2 ± 5.7 kg, respectively, in the D group; -2.4 ± 3.2 and -2.7 ± 5.9 kg, respectively, in the E group; -6.9 ± 3.0 and -7.3 ± 6.3 kg, respectively, in the DE group; and -0.8 ± 3.0 and -0.9 ± 6.6 kg, respectively, in the C group. The main effects of D treatment, but not of E treatment, on weight were significant at both times (P < 0.001)., Conclusions: Dietary treatment provided clinically relevant weight loss in lactating postpartum women, which was sustained at 9 mo after treatment. The combined treatment did not yield significant weight or body-composition changes beyond those of dietary treatment alone. more...

Objective: To identify predictive factors for initiation and maintenance of breastfeeding with a focus on mothers with type 1 diabetes., Research Design and Methods: This is a prospective observation survey, using a case-control design, comparing the outcomes of 108 mothers with type 1 diabetes with 104 mothers without diabetes that were matched for parity and gestational age. Mother and infant outcomes were collected from medical records and through telephone interviews 2 and 6 months after delivery. Predictive factors were calculated by logistic regression analyses., Results: Mothers with diabetes were less likely to partly or exclusively breastfeed their children at 2 months (OR 0.42 [95% CI 0.18-0.96], P = 0.041) and 6 months (0.50 [0.27-0.90], P = 0.022) than mothers without diabetes. On multivariable analysis, type 1 diabetes did not remain an independent predictive factor. Instead, higher education level and breastfeeding at discharge from hospital were predictive factors for breastfeeding at 2 months postpartum. These variables as well as delivery >37 weeks and early breastfeeding predicted breastfeeding 6 months postpartum., Conclusions: Factors associated with maternal diabetes, such as problems with establishing breastfeeding in the early postpartum period, affects the likelihood of long-term breastfeeding. more...

Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes., (Copyright © 2010 Elsevier Ltd. All rights reserved.) more...

Inhibition of mammalian target of rapamycin (mTOR) signaling in cultured human primary trophoblast cells reduces the activity of key placental amino acid transporters. However, the upstream regulators of placental mTOR are unknown. We hypothesized that glucose, insulin, and IGF-I regulate placental amino acid transporters by inducing changes in mTOR signaling. Primary human trophoblast cells were cultured for 24 h with media containing various glucose concentrations, insulin, or IGF-I, with or without the mTOR inhibitor rapamycin, and, subsequently, the activity of system A, system L, and taurine (TAUT) transporters was measured. Glucose deprivation (0.5 mM glucose) did not significantly affect Thr172-AMP-activated protein kinase phosphorylation or REDD1 expression but decreased S6 kinase 1 phosphorylation at Thr389. The activity of system L decreased in a dose-dependent manner in response to decreasing glucose concentrations. This effect was abolished in the presence of rapamycin. Glucose deprivation had two opposing effects on system A activity: 1) an "adaptive" upregulation mediated by an mTOR-independent mechanism and 2) downregulation by an mTOR-dependent mechanism. TAUT activity was increased after incubating cells with glucose-deprived media, and this effect was largely independent of mTOR signaling. Insulin and IGF-I increased system A activity and insulin stimulated system L activity, effects that were abolished by rapamycin. We conclude that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta. more...

Objective: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease., Design: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included., Setting: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery., Participants: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100., Main Outcome Measures: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone., Results: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations more...

Background: Obese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established., Objective: We aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight., Design: Pregnant women with BMIs (in kg/m(2)) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8-12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors., Results: We found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight., Conclusions: High first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport. more...

Background: This study describes maternal and neonatal characteristics and delivery outcome in women with gestational diabetes mellitus [GDM], compared to a control group., Methods: A retrospective observational study of 719 women with GDM was undertaken in a Swedish urban district. All other parturients at the same hospital served as the control group. GDM was diagnosed using random capillary glucose levels at fixed intervals, beginning early in pregnancy. An oral glucose tolerance test was performed at glucose levels>or=7.0 mmol/l (127.8 mg/dl). Data was analysed according to glucose levels at diagnosis, ie, mild or severe GDM., Results: GDM was diagnosed in 2.28% of the women who were older and had higher Body Mass Index [BMI]. A high proportion was of non-Nordic origin (44.5%); they had severe GDM more often (49.1%) than the Nordic group (33.1%). The GDM-mild group had less complications and abnormalities, compared to the GDM-severe group, although both groups differed from the control group in this respect. Delivery was spontaneous in 70.2% of GDM-mild, 65.7% of GDM-severe and 81.0% of the control group. LGA (+2 SD) was found in 4.8, 10.5 and 3.2%, respectively., Conclusion: Early non-fasting random universal screening and multidisciplinary antenatal teamwork intervention seems to be favourable, with low rates of excessive fetal growth, instrumental vaginal delivery and caesarean section. more...

Background: To evaluate the association between obstetric brachial plexus palsy and obstetrical maneuvers during the second stage of delivery., Methods: Prospective population-based case control study. Cases of obstetric brachial plexus palsy were compared with a randomly selected control group with regard to obstetric management., Results: Five or more obstetrical maneuvers were used to deliver the infants in 82% in the obstetric brachial plexus palsy group versus 1.8% in the controls. Risk factors independently associated with obstetric brachial plexus palsy were force applied when downward traction was imposed on the fetal head (odds ratio 15.2; 95% confidence interval 8.4-27.7). The incidence of obstetric brachial plexus palsy in the infants in the population was 3.3 per thousand. At 18 months of age 16.1% (incidence of 0.05%) of children had residual functional deficits and downward traction with substantial force was applied in all these cases., Conclusions: Forceful downward traction applied to the head after the fetal third rotation represents an important risk factor of obstetric brachial plexus palsy in vaginal deliveries in cephalic presentation. more...

Objective: The purpose of this study was to monitor the introduction of the STAN-methodology (Noventa Medical, Moelndal, Sweden)., Study Design: This was a prospective observational study covering the total population of deliveries at term during 2 years. Four thousand eight hundred and thirty out of 14,687 term pregnancies were monitored using the STAN S 21 fetal heart monitor and the associated clinical guidelines. Cord artery metabolic acidosis, neonatal outcome, and rates of operative deliveries for fetal distress were assessed., Results: The annual rate of STAN usage increased from 28.1% to 37.7% and was associated with a significant reduction in metabolic acidosis rate in the total population from 0.76% to 0.44% (P < .05). The compliance with the clinical guidelines increased in cases requiring intervention. The rates for moderate/severe hypoxic neonatal encephalopathy were consistently low, 0.55 and 0.68 per 1000 deliveries, respectively, and corresponding to previous findings. The rate of operative delivery did not change during the 2 years in the total population., Conclusion: Increasing STAN usage provided consistent improvements in fetal outcome equalling those noted in the Swedish randomized controlled trial (RCT) without increasing operative interventions for fetal distress. more...

Triglyceride (TG) hydrolases in the placental microvillous plasma membrane (MVM) release fatty acids from circulating lipoproteins and represent the critical initial step in transplacental fatty acid transfer. We investigated the activity of two TG hydrolases in MVM isolated from placentas of appropriately grown for gestational age pregnancies and pregnancies complicated by intrauterine growth restriction (IUGR), insulin-dependent diabetes mellitus (IDDM) or gestational diabetes mellitus (GDM). In addition, we measured protein expression of lipoprotein lipase (LPL) in MVM and two fatty acid binding proteins (L- and C-FABP) in placental homogenates. The TG hydrolase activities were assessed by measuring hydrolysis of (3)H-trioleic acid incorporated into intralipid micelles after incubation with MVM. The placenta-specific TG hydrolase activity (optimum at pH 6) did not differ in the patient groups studied. MVM LPL activity (optimum at pH 8) was reduced by 47% in preterm IUGR (n = 8, P < 0.05), compared with gestational age-matched controls. The LPL activity in placentas of IDDM pregnancies was increased by 39% (n = 8, P < 0.05), compared with controls. No significant differences were observed in cases of GDM. We found no alteration in protein expression of LPL or C-FABP. The expression of L-FABP was increased by 112% (n = 8, P < 0.05) in IDDM and 64% (n = 8, P < 0.05) in GDM. These results indicate that alterations in MVM LPL activity and expression of L-FABP may contribute to the altered lipid deposition and metabolism in IUGR and diabetic pregnancies. more...

Many fetuses suffering from intrauterine growth restriction (IUGR) are hypoglycaemic. However, the underlying mechanisms are not well established. An increased placental glucose consumption in IUGR could impair glucose transfer across the placenta. In this study we used two different approaches to investigate glucose metabolism in preterm and term placentae of IUGR fetuses. We determined activity and protein expression of the three rate-limiting glycolytic enzymes phosphofructo kinase (PFK), pyruvate kinase (PK) and hexokinase (HXK) in a cytoplasmic fraction of homogenates of placentae obtained from IUGR and appropriate for gestational age (AGA) pregnancies. Protein expression was assessed using Western blot and enzyme activities were determined in a spectrophotometer by measuring the rate of NADH oxidation (PFK and PK) or NADP reduction (HXK) in enzyme reactions coupled to the respective enzyme. To determine the distribution of the glycolytic enzymes immunocytochemistry was performed. We also measured glucose consumption and lactate production in fresh placental villous tissue using a perifusion system. The expression of PFK, PK and HXK as well as the activity of PK and HXK was unaltered in IUGR placentae. The activity of PFK on the other hand was 32 per cent lower in IUGR placentae (n=24, P<0.05). Immunocytochemistry confirmed the distribution of the enzymes to the cytoplasm of the syncytiotrophoblast. Placental glucose consumption in IUGR [0.06+/-0.01 micromol/(min*g), n=5] was not different from AGA [0.06+/-0.005 micromol/(min*g), n=12], whereas lactate production was decreased by 28 per cent in IUGR. These results do not support the hypothesis of increased placental glucose consumption but suggest an altered glycolytic pathway in the IUGR placenta. more...

The reduced fetal growth in intrauterine growth restriction (IUGR) has been attributed to decreased placental blood flow whereas maternal hyperglycemia is believed to represent the primary cause of accelerated fetal growth in pregnancies complicated by diabetes. However, recent research has demonstrated specific changes in placental transport function in association to these pregnancy complications that are likely to contribute to the altered fetal growth patterns. For example, in IUGR the activity of certain key amino acid transporters is reduced in the placental barrier and accelerated fetal growth in diabetes is associated with an increased activity of placental glucose and amino acid transporters. Therefore, placental insufficiency in IUGR is not just a question of reduced placental blood flow and up-regulation of placental nutrient transporters in diabetes may explain the high incidence of accelerated fetal growth despite rigorous maternal glycemic control. more...

In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is distributed to both the microvillous membrane (MVM) and the basal membrane (BM) of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in maintaining the electrochemical gradient for Na(+), which represents the driving force for Na(+)-coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na(+)-coupled transporters and contribute to the reduced growth of these fetuses. more...

Neonates born after pregnancies complicated by diabetes or intrauterine growth restriction (IUGR) have increased incidence of hypocalcaemia. Furthermore, IUGR is associated with reduced bone mineralization in infancy and osteoporosis in adult life. We tested the hypothesis that placental calcium transport is altered in these pregnancy complications. Transport of calcium into syncytiotrophoblast basal plasma membrane (BM) vesicles was studied by rapid filtration and protein expression of Ca(2+) ATPase by Western blot. In IUGR Ca(2+) ATPase activity was increased by 48 per cent (n=13; P< 0.05) whereas protein expression was 15 per cent lower (n=13; P< 0.05) than in controls (n=16). Basal membrane ATP dependent calcium transport was unaltered in gestational diabetes (GDM) but increased by 54 per cent in insulin dependent diabetes (IDDM) compared to controls (P< 0.05; n =14). Diabetes did not affect Ca(2+) ATPase expression in BM. We have previously shown that the mid-molecular fragment of parathyroid hormone related peptide (PTHrP midmolecule) stimulates BM Ca(2+) ATPase in vitro. PTHrP midmolecule concentrations in umbilical cord plasma were measured using radioimmunoassay. The concentrations in umbilical cord plasma were increased in IUGR, but unaltered in diabetes. In conclusion, placental calcium pump is activated in IUGR and IDDM, which may be secondary to increased foetal calcium demand. We speculate that PTHrP midmolecule may be one mechanism for activating BM Ca(2+) ATPase in IUGR. more...

Alterations in placental transport may contribute to accelerated fetal growth in pregnancies complicated by diabetes. We studied the activity of the syncytiotrophoblast amino acid transporter system A and the transport of the essential amino acids leucine, lysine, and taurine. Syncytiotrophoblast microvillous plasma membranes (MVMs) and basal plasma membranes (BMs) were isolated from placentas obtained from normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and type 1 diabetes, with and without large-for-gestational-age (LGA) fetuses. Amino acid transport was assessed using radio-labeled substrates and rapid filtration techniques. System A activity in MVM was increased (65-80%, P < 0.05) in all groups with diabetes independent of fetal overgrowth. However, MVM system A activity was unaffected in placentas of normal pregnancies with LGA fetuses. MVM leucine transport was increased in the GDM/LGA group. In BMs, amino acid transport was unaffected by diabetes. In conclusion, diabetes in pregnancy is associated with an increased system A activity in MVM, and MVM leucine transport is increased in the GDM/LGA group. We suggest that these changes result in an increased uptake of neutral amino acids across MVM, which may be used in placental metabolism or be delivered to the fetus. The increased MVM leucine uptake in the GDM/LGA group may contribute to accelerated fetal growth in these patients. more...

The mechanisms underlying the reduced fetal plasma concentrations of amino acids and glucose associated with intrauterine growth restriction (IUGR) remain to be fully established. The activity of the amino acid transporter system A has been shown to be reduced in the syncytiotrophoblast microvillous membrane (MVM) in IUGR, however the impact of these changes on transplacental transport is difficult to assess without information on system A activity in the basal plasma membrane (BM). In this study we measured system A activity and mediated D-glucose uptake using radiolabelled substrates and rapid filtration techniques, and glucose transporter isoform 1 (GLUT 1) protein expression using Western blots in MVM and BM isolated from human placentas. In term IUGR (n=11) MVM system A activity was unaltered compared to controls (n=9). In contrast, system A activity in MVM was reduced by 50 per cent (P< 0.05) in preterm IUGR (n=8, gestational age 28-36 weeks) as compared to controls (n=8, gestational age 28-35 weeks). BM system A activity was unaltered in both IUGR groups. Similarly, MVM and BM GLUT 1 expression and mediated D-glucose uptake was not affected by IUGR. In all preterm IUGR pregnancies signs of severe fetal compromise were present whereas term IUGR fetuses were less affected. These data support the view that MVM system A activity is related to the severity of compromise in IUGR. The markedly reduced system A activity in MVM in preterm IUGR together with the unaltered activity in BM is consistent with a decreased transplacental transport of neutral amino acids in this pregnancy complication. The hypoglycemia present in utero in some IUGR fetuses is not caused by a decreased glucose transport capacity across the syncytiotrophoblast plasma membranes., (Copyright 2002 Elsevier Science Ltd. All rights reserved.) more...

During normal pregnancy, a predominance of Th2 type cytokines prevails and is considered to protect the fetus. Animal experiments suggest that an increase of Th1 type cytokines may instead have deleterious effects. We have studied with the reverse transcription PCR technique mRNA for IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, tumor necrosis factor-alpha, and interferon-gamma in placentas from full-term appropriately grown newborns, newborns with intrauterine growth retardation (IUGR) and newborns who were only small for gestational age. The mRNA for IL-10 was significantly reduced in the IUGR placentas (p < 0.05), whereas the mRNA for IL-8 was significantly higher (p < 0.05) for the IUGR cases compared with the full-term neonates. It might be that reduced IL-10 in the placenta is involved in the pathogenesis of IUGR. more...

Background: The objectives were 1. to evaluate if the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine was altered in mild and severe forms of preeclampsia, and 2. to assess the relationship between dimethylarginines and the cytokine response in preeclampsia., Methods: Asymmetric and symmetric dimethylarginine were measured with high performance liquid chromatography in women with mild (n=13) and severe (n=32) preeclampsia and in normotensive pregnant controls (n=20). Interleukin-4, -6, -8, -10 and tumor necrosis factor-alpha were analyzed by immunoassays in women with mild (n=8) and severe (n=17) preeclampsia and in normotensive pregnant controls (n=14). The Mann Whitney U-test and Spearman Rank test were used for statistical analysis., Results: The plasma levels of dimethylarginine were increased in preeclamptic subjects. The elevation of symmetric dimethylarginine was more pronounced than that of asymmetric dimethylarginine. The control levels of interleukin-6, -8 and -10 were significantly higher at term than at gestational week 32-36. Interleukin-6 and -8 were significantly elevated in subjects with severe, but not mild, preeclampsia, whereas TNF-alpha and IL-10 were not significantly altered. Symmetric dimethylarginine levels correlated significantly with arterial blood pressure and serum levels of creatinine and uric acid. Dimethylarginine levels in plasma were, however, not related to the cytokine response., Conclusions: Plasma concentrations of both asymmetric and symmetric dimethylarginine were significantly elevated both in mild and severe preeclampsia. Symmetric, but not asymmetric, dimethylarginine correlated to the severity of the condition. Plasma levels of interleukin-6 and -8 were also elevated in severe preeclampsia but no direct correlations were found between these cytokines and dimethylarginines. more...

Objective: We have previously reported that type 1 diabetes mellitus with hyperglycemia during the first trimester is associated with an up-regulation of placental glucose transport at term. We speculated that glucose concentrations regulate placental glucose transporters only during early pregnancy. To test this hypothesis we studied placental glucose transport in gestational diabetes mellitus, which is associated with hyperglycemia mainly during the second half of pregnancy., Study Design: Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles were isolated from uneventful pregnancies (control group, n = 32) and pregnancies complicated by gestational diabetes mellitus (n = 18). Glucose uptake and glucose transporter 1 expression were studied by means of radiolabeled tracers and Western blotting, respectively., Results: Gestational diabetes mellitus was not associated with alterations in placental glucose transport. Separate analysis of 6 patients in the gestational diabetes mellitus group with large-for-gestational-age babies did not affect these results., Conclusion: These findings are consistent with the hypothesis that the sensitivity of placental glucose transporters to regulation by nutrient availability is limited to early pregnancy. more...

The objective of this study was to determine placental membrane permeabilities to water, urea and mannitol in intrauterine growth restriction (IUGR) and compare them to normal gestational age matched controls. Further, we wished to investigate whether potential changes in permeability were related to changes in membrane fluidity, cholesterol or phospholipid fatty acid content of the membranes. Syncytiotrophoblast microvillous (MVM) and basal membranes (BM) were isolated from normal and IUGR placentas at term. Passive permeability to water, urea, and mannitol showed no significant alterations in IUGR compared to controls. Cholesterol content in BM, but not in MVM, was lower in placentas from pregnancies complicated by IUGR. However, membrane fluidity did not change in these pregnancies. The phospholipid fatty acid composition of the plasma membranes isolated from all placentas showed a predominance of unsaturated fatty acid species in the BM and saturated species in the MVM. In the MVM from IUGR, mead acid (20:3), behenic acid (22:0) and nervonic acid (24:1) constituted higher percentages of the total when compared to normally grown controls. In the BM from IUGR, mead acid (20:3) was increased relative to the total phospholipid fatty acid content. In conclusion, the syncytiotrophoblast membranes exhibit only minor changes in passive permeability and composition when the pregnancy is complicated by IUGR. more...

Objective: Altered transport functions in the placenta might contribute to adverse outcome of pregnancies in women with diabetes. Therefore we studied placental glucose transport in this pregnancy complication., Study Design: Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles were isolated from women with uneventful pregnancies (control subjects, n = 21) and from women with pregnancies complicated by insulin-dependent diabetes mellitus, White class D (n = 7). Glucose uptake and GLUT 1 (glucose transporter 1) expression were studied by means of radiolabeled tracers and Western blot, respectively., Results: In the group with insulin-dependent diabetes mellitus, values for hemoglobin A1c were moderately elevated in the first trimester (6.61 +/- 0.35) but not later in pregnancy and 4 of the 7 neonates were large for gestational age. In the basal membrane vesicles, insulin-dependent diabetes mellitus was associated with a 40% increase in GLUT 1 expression and a 59% higher mediated uptake of d -glucose. No alterations could be demonstrated in microvillus membrane vesicles., Conclusion: Placental glucose transport capacity appears to be increased in insulin-dependent diabetes mellitus. These alterations might explain the occurrence of macrosomia despite well-controlled diabetes. more...

Objective: To compare gestational age (GA) calculated from oocyte retrieval and from ultrasound measurements in pregnancies after in vitro fertilization (IVF)., Design: In a retrospective study of 253 women with singleton and 84 women with twin pregnancies conceived from IVF, GA calculated from the day of oocyte retrieval was compared with GA calculated in the second trimester of pregnancy from ultrasound measurements of biparietal diameter (BPD) and femur length (FL)., Results: For singletons, the mean GA calculated from ultrasound measurements was significantly shorter than the mean GA estimated from the day of oocyte retrieval. The mean difference was 1.9 days (SD 3.3; 95% CI 1.5-2.4) if only BPD was used and 2.1 days (SD 2.1; 95% CI 1.6-2.5) if BPD and FL were combined. For twins, the mean GA calculated from ultrasound measurements was also significantly shorter than the mean GA calculated from the day of oocyte retrieval. The mean difference was 1.4 days (SD 2.7; 95% CI 1.0-1.8) if BPD was used and 1.6 days (SD 2.5; 95% CI 1.2-2.0) if BPD and FL were combined., Conclusions: In IVF pregnancies, term prediction using ultrasound in the second trimester is reliable and may reduce the number of pregnancies subsequently classified as post-term, thus avoiding unnecessary obstetric interventions. more...

Background: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies., Methods: 255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores., Findings: Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively., Interpretation: The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age. more...