Socioeconomic inequities during COVID 19 pandemic increase preterm birth and low birth weight in the most underprivileged.

BACKGROUND: The mitigation measures implemented to face the healthcare emergency brought by COVID 19 pandemic generated an increase in socioeconomic inequities in the most underprivileged population which is also the most threatened in their human rights. In Uruguay, this population is assisted in the public health care system. To analyze how these measures impacted on these mothers and their neonates we selected outcomes that most contributed to neonatal mortality. OBJECTIVE: To analyze the incidence of Preterm Birth (PB), Intrauterine Growth Restriction (IUGR) and Low Birth Weight (LBW) in the public health care system in Uruguay, during the period of time in which the strictest measures were adopted to mitigate the COVID 19 pandemic in 2020 (para-pandemic period) compared to the same period in 2019 (pre-pandemic). METHODS: A retrospective, cross sectional, descriptive study was performed to compare PB, IUGR and LBW from 15 March to 30 September 2019 (before COVID 19 pandemic) to the same period of 2020 (when COVID 19 pandemic bloomed), in the public health care subsystem. The analysis was performed with data from the national perinatal database system (SIP). RESULTS: In 2020, a significative increase in PB, RR: 1.14 (CI 95%: 1.03-1.25), and in LBW, RR: 1.16 (CI 95% 1.02-1.33), was registered compared to 2019 (pre-pandemic period). IUGR also showed an increase, but without statistical significance (4.6% in 2019 vs 5.2% in 2020, RR 1.13 CI 95% 0.98-1.31). The compared groups showed no differences in the distribution of biological confounding variables that could explain the increase in incidence of the main outcomes. CONCLUSIONS: In the absence of other factors that could explain the results we consider that social crisis associated to the restrictive measures implemented in the country to dwindle the effect of the pandemic exacerbated the adverse conditions that affect the reproductive process for those underprivileged women assisted in the public sector, increasing PB and LBW. It is important to consider the future impact of these results on neonatal and infant mortality and to implement social measures to reduce the damage as soon as possible.

Higher PAPP-A Values in Pregnant Women Complicated with Preeclampsia Than with Gestational Hypertension.

The purpose of this study is to compare the levels of maternal serum pregnancy-associated plasma protein-A at the first trimester in pregnancies complicated by impaired placental diseases, such as preeclampsia (PE), intrauterine fetal growth restriction (IUGR), and gestational hypertension (GH), with those in pregnancies without the development of any of these outcomes to expand the knowledge of how this protein behaves in the different impaired placental diseases. This current work is an observational study based on a prospective cohort. Pregnancy-associated plasma protein-A was measured in 422 patients who had completed maternal-perinatal outcomes. Comparisons of pregnancy characteristics and the biomarker between outcome groups (PE, IUGR, gestational hypertension, and not impaired placental outcomes) were analyzed. PAPP-A MoM in the IUGR (0.8 IQR: 0.6-0.9) and GH groups (0.5 IQR: 0.3-1.4) compared to the PE group (1.06 IQR: 0.66-1.52) was significantly lower (p < 0.005). Pregnant women who developed early-onset PE (1.11 IQR 1.08-1.18) presented significant differences with the IUGR group (0.83 IQR: 0.59-0.98; p = 0.002) and those who developed preterm-PE (1.19 IQR: 0.66-1.58; p = 0.045). The results demonstrate that the levels of PAPP-A at first trimester in the sample of women who developed PE, and specially term-PE, were higher than those in women who developed GH or IUGR. The GH group had the lowest PAPP-A values in this sample of pregnant women. Research in a population with a high prevalence of preeclampsia is still lacking and deserves more extended studies to define if these patients could have different rates of PAPP-A.

Restrição intrauterina de crescimento: conhecendo seus efeitos sobre o plantel de reprodução / Intrauterine growth restriction: knowing its effects on the breeding herd

A restrição intrauterina de crescimento (RIUC) é a condição na qual o feto não expressa o seu potencial de crescimento de acordo com a idade gestacional. Tal condição ocorre naturalmente na espécie suína, no entanto apresenta forma muito severa, trazendo sérios prejuízos à cadeia suinícola. Os efeitos deletérios da RIUC sobre parâmetros zootécnicos estão bem estabelecidos. No entanto, o conhecimento de tais efeitos sobre parâmetros reprodutivos em machos e fêmeas ainda é limitado. Portanto, a presente revisão tem por objetivo compilar os estudos sobre efeitos da RIUC em parâmetros reprodutivos em machos e fêmeas, bem como intervenções propostas para a diminuição da incidência da condição e de seus efeitos. Achados nesse assunto fornecerão informações valiosas acerca da morfofisiologia reprodutiva de suínos RIUC, estabelecendo estratégias para minimizar as perdas econômicas para o sistema de produção.(AU)

Intrauterine growth restriction (IUGR) is the condition in which the fetus does not express its growth potential according to the gestational age. This condition naturally occurs in the swine species. However, it is very severe and can cause serious losses to the swine production chain. The deleterious effects of IUGR on zootechnical parameters are well established. However, the knowledge of such effects on reproductive parameters in males and females is still limited. Therefore, the present review aims to compile the studies on the effects of IUGR on reproductive parameters in males and females, as well as proposed interventions to decrease the incidence of the condition and its effects. Findings on this issue will provide valuable information about the reproductive morphophysiology of IUGR pigs, establishing strategies to minimize economic losses to the production system.(AU)

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats.

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.

Assessing the Role of Uric Acid as a Predictor of Preeclampsia.

We assessed the diagnostic utility of uric acid for the prediction of preeclampsia. An observational prospective approach was carried out during 2014. Preeclamptic women were classified into 4 groups accordingly to the onset of preeclampsia and the presence of intrauterine growth restriction (IUGR). Serum uric acid levels, urea, and creatinine were measured. Receiver operating curves (ROC) of the uric acid levels ratio (UAr) between a dosage before and after the 20th week of gestation were performed. One thousand two hundred and ninety-third pregnant women were enrolled in this study. Eight hundred ten had non-complicated pregnancies, 40 preeclampsia, 33 gestational hypertension, and 20 IUGR without preeclampsia. Uric acid significantly raised after 20 weeks of gestation in women who develop preeclampsia before 34 weeks (Group A) or in those who develop preeclampsia after 37 weeks associated with IUGR (Group C). In women who develop preeclampsia after 34 weeks without IUGR (Groups B and D), uric acid increased after the 30th week of gestation. In all groups, UAr was greater than 1.5. In gestational hypertension, UAr was superior to 1.5 toward the end of gestation, while in IUGR without preeclampsia, the behavior of serum uric acid was similar to non-complicated pregnancies. In all cases, urea and creatinine showed normal values, confirming that patients had no renal compromise. ROC area was 0.918 [95% confidence interval (CI): 0.858-0.979) for the preeclampsia group and 0.955 (95% CI: 0.908-1.000) for Group A. UAr at a cut-off point ≥1.5 had a very low positive predictive value, but a high negative predictive value of 99.5% for preeclampsia and it reached 100% for Group A. Thus, a UAr less than 1.5 may be a helpful parameter with a strong exclusion value and high sensitivity for those women who are not expected to develop preeclampsia. Additionally, this low-cost test would allow for better use of resources in developing countries.

Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort

Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Fructose consumption by rodents modulates both hepatic and intestinal lipid metabolism and gluconeogenesis. We have previously demonstrated that in utero exposure to dexamethasone (DEX) interacts with fructose consumption during adult life to exacerbate hepatic steatosis in rats. The aim of this study was to clarify if adult rats born to DEX-treated mothers would display differences in intestinal gluconeogenesis after excessive fructose intake. To address this issue, female Wistar rats were treated with DEX during pregnancy and control (CTL) mothers were kept untreated. Adult offspring born to CTL and DEX-treated mothers were assigned to receive either tap water (Control-Standard Chow (CTL-SC) and Dexamethasone-Standard Chow (DEX-SC)) or 10% fructose in the drinking water (CTL-fructose and DEX-fructose). Fructose consumption lasted for 80 days. All rats were subjected to a 40 h fasting before sample collection. We found that DEX-fructose rats have increased glucose and reduced lactate in the portal blood. Jejunum samples of DEX-fructose rats have enhanced phosphoenolpyruvate carboxykinase (PEPCK) expression and activity, higher facilitated glucose transporter member 2 (GLUT2) and facilitated glucose transporter member 5 (GLUT5) content, and increased villous height, crypt depth, and proliferating cell nuclear antigen (PCNA) staining. The current data reveal that rats born to DEX-treated mothers that consume fructose during adult life have increased intestinal gluconeogenesis while recapitulating metabolic and morphological features of the neonatal jejunum phenotype.

Hyperlipidic diet affects body composition and induces anxiety-like behaviour in intrauterine growth-restricted adult mice.

NEW FINDINGS: What is the central question of this study? What is the effect in male and female offspring of a protein-deficient diet producing intrauterine growth restriction (IUGR) in maternal mice on morphometric, metabolic and behavioural parameters before and after a challenge with a fat diet? What is the main finding and its importance? Male and female mice presented different growth trajectories after birth. IUGR favoured increased adiposity in male mice, and high-fat diet-induced anxiety-like behaviour in female mice. ABSTRACT: As there is sexual dimorphism in the response to maternal manipulations, we aimed to analyse the effects of intrauterine growth restriction (IUGR) in both sexes on morphometric, metabolic and behavioural parameters throughout postnatal development, and after challenge with a hyperlipidic diet. Female Swiss mice (n = 59) were distributed into two groups (SD: standard diet, n = 26; and PDD: isocaloric protein-deficient diet, n = 33), 2 weeks before mating and during the gestational period. After birth, offspring from SD and PDD dams were cross-fostered and nurtured by SD dams until postnatal day (PND) 28. At PND 60 all animals were challenged with a hypercaloric diet for 4 weeks. Offspring birth weight was significantly reduced in the PDD group compared to the SD group (P = 0.0001), but only male offspring presented a rapid catch-up during the first 21 days of development. Although no differences in body weight were observed between groups after the challenge with the hyperlipidic diet, an increase in the relative perigonadal white adipose tissue (P = 0.009) and a decrease in gross gastrocnemius muscle weight (P = 0.010) were observed in the PDD males. In relation to behavioural tests, there was an increase in locomotion in both sexes (P = 0.0001), and a decrease in female grooming (P = 0.006) in the PDD group. Additionally, females from the PDD group showed increased hyperlipidic food intake. In conclusion, IUGR affected both sexes, with females showing prominent behavioural modifications and males presenting altered body composition elicited by a hyperlipidic diet.

A Proxy for Detecting IUGR Based on Gestational Age Estimation in a Guatemalan Rural Population.

In-utero progress of fetal development is normally assessed through manual measurements taken from ultrasound images, requiring relatively expensive equipment and well-trained personnel. Such monitoring is therefore unavailable in low- and middle-income countries (LMICs), where most of the perinatal mortality and morbidity exists. The work presented here attempts to identify a proxy for IUGR, which is a significant contributor to perinatal death in LMICs, by determining gestational age (GA) from data derived from simple-to-use, low-cost one-dimensional Doppler ultrasound (1D-DUS) and blood pressure devices. A total of 114 paired 1D-DUS recordings and maternal blood pressure recordings were selected, based on previously described signal quality measures. The average length of 1D-DUS recording was 10.43 ± 1.41 min. The min/median/max systolic and diastolic maternal blood pressures were 79/102/121 and 50.5/63.5/78.5 mmHg, respectively. GA was estimated using features derived from the 1D-DUS and maternal blood pressure using a support vector regression (SVR) approach and GA based on the last menstrual period as a reference target. A total of 50 trials of 5-fold cross-validation were performed for feature selection. The final SVR model was retrained on the training data and then tested on a held-out set comprising 28 normal weight and 25 low birth weight (LBW) newborns. The mean absolute GA error with respect to the last menstrual period was found to be 0.72 and 1.01 months for the normal and LBW newborns, respectively. The mean error in the GA estimate was shown to be negatively correlated with the birth weight. Thus, if the estimated GA is lower than the (remembered) GA calculated from last menstruation, then this could be interpreted as a potential sign of IUGR associated with LBW, and referral and intervention may be necessary. The assessment system may, therefore, have an immediate impact if coupled with suitable intervention, such as nutritional supplementation. However, a prospective clinical trial is required to show the efficacy of such a metric in the detection of IUGR and the impact of the intervention.

Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals / A vontade de se exercitar é programada ainda no útero? Análise do comportamento sedentário e dos benefícios da atividade física em indivíduos com crescimento intrauterino restrito

Abstract Objective: The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. Sources: PubMed, Scielo, Scopus and Embase. Summary of findings: Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. Conclusions: Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR.

Resumo Objetivo: A literatura sugere que um feto se adaptará às adversidades externas ao aprimorar seu gasto energético para melhorar a sobrevida, o que leva, em última instância, à programação do consumo e gasto energético do indivíduo. Apesar de análises recentes terem focado na programação fetal do consumo energético e preferências alimentares, ainda há alguma comprovação de que as adversidades fetais estão associadas aos baixos níveis de atividade física. Portanto, visamos a analisar: a) a comprovação de uma associação entre nascer com restrição de crescimento intrauterino (RCIU) e sedentarismo durante o curso de vida e b) os possíveis benefícios da atividade física sobre os fatores de risco cardiometabólico dessa população. Fontes: PubMed, Scielo, Scopus e Embase. Resumo dos achados: A maior parte dos estudos clínicos que usaram medidas objetivas não constatou associação entre RCIU e os níveis de atividade física, ao passo que a maior parte dos estudos que usaram questionários de autorrelato revelou essas relações, principalmente no que diz respeito à atividade física de lazer. Estudos experimentais corroboram a existência de programação fetal de atividade física e mostram que a exposição a exercícios durante a vida de indivíduos com RCIU melhora os resultados metabólicos, porém menos efeito foi visto sobre a arquitetura ou função muscular. Conclusões: Alterações na força muscular e no metabolismo, bem como o desempenho aeróbico alterado, podem predispor indivíduos com RCIU a serem espontaneamente menos ativos fisicamente, sugere que essa população pode ser um importante alvo de intervenções preventivas. Apesar de muito heterogêneos, os diferentes estudos nos possibilitam deduzir que a atividade física pode ter efeitos benéficos principalmente em indivíduos mais vulneráveis a modificações metabólicas, como aqueles com RCIU.

Maternal carriers of the ANXA5 M2 haplotype are exposed to a greater risk for placenta-mediated pregnancy complications.

PURPOSE: Annexin A5 (ANXA5) is a protein abundantly expressed in normal placenta where it contributes to the healthy outcome of a pregnancy. Lower ANXA5 levels have been observed in M2/ANXA5 haplotype carrying chorion. Consequently, this study aimed to assess the potential association of M2 maternal carrier status with the risk of recurrent pregnancy loss (RPL), the timing of miscarriages, and other obstetric complications, for the first time in a population from Latin America. METHODS: This study was designed as a prospective recruitment of RPL patients with post hoc analysis. The distribution of the M2/ANXA5 haplotype was compared between a group of 229 Argentine women with RPL and 100 parous controls, and was further analyzed in subgroups of patients stratified according to the timing of miscarriages and in relation to other obstetric complications. RESULTS: No significant differences were found in the distribution of M2 haplotype among either RPL patients or the subgroups with embryonic, early fetal, or late fetal losses compared to parous controls. Notwithstanding, maternal M2/ANXA5 was found to be independently associated with a higher risk of suffering intrauterine growth restriction (IUGR) and/or preeclampsia (PE). Simultaneously, the presence of inherited and/or acquired thrombophilia also proved to be an independent risk factor for these. CONCLUSIONS: The association found between the maternal carriage of the M2/ANXA5 haplotype and an elevated risk of IUGR and/or PE supports the hypothesis that carrier status of this haplotype and the consequently reduced placental ANXA5 expression might be responsible, at least partially, for the onset of these gestational vascular complications.

Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals.

OBJECTIVE: The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. SOURCES: PubMed, Scielo, Scopus and Embase. SUMMARY OF FINDINGS: Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. CONCLUSIONS: Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR.

Psychologic intimate partner violence and the risk of intrauterine growth restriction in Rio de Janeiro.

OBJECTIVE: To evaluate whether psychologic intimate partner violence (IPV) during pregnancy is a risk factor for intrauterine growth restriction (IUGR). METHODS: The cross-sectional study enrolled randomly selected mothers of infants younger than 5 months attending basic health services in Rio de Janeiro, Brazil, from January to July 2007. Psychologic and physical IPV were evaluated by the Revised Conflict Tactics Scale; IUGR was defined as below the 10th percentile of the Alexander curve. Socioeconomic status, housing conditions, stressful events, life habits, social support, and medical information were obtained by interview or from medical records. Multivariate hierarchical logistic regression models, taking into account potential confounders, were used to evaluate the relationship between mounting acts of psychologic IPV and IUGR. RESULTS: There were 810 women included in the study. Psychologic IPV during pregnancy was reported by 665 women (82.1%) and 126 newborns (15.6%) showed growth restriction. In the final model, each 1-unit increase in psychologic IPV score during pregnancy led to a 15% higher risk of IUGR at birth (odds ratio 1.15; P<0.001). CONCLUSION: Psychologic IPV during pregnancy seems to be a significant and independent risk factor for IUGR. This finding reinforces the importance of preventive and intervention procedures for IPV to reduce adverse perinatal outcomes.

Agile Development of a Smartphone App for Perinatal Monitoring in a Resource-Constrained Setting.

Technology provides the potential to empower frontline healthcare workers with low levels of training and literacy, particularly in low- and middle-income countries. An obvious platform for achieving this aim is the smartphone, a low cost, almost ubiquitous device with good supply chain infrastructure and a general cultural acceptance for its use. In particular, the smartphone offers the opportunity to provide augmented or procedural information through active audiovisual aids to illiterate or untrained users, as described in this article. In this article, the process of refinement and iterative design of a smartphone application prototype to support perinatal surveillance in rural Guatemala for indigenous Maya lay midwives with low levels of literacy and technology exposure is described. Following on from a pilot to investigate the feasibility of this system, a two-year project to develop a robust in-field system was initiated, culminating in a randomized controlled trial of the system, which is ongoing. The development required an agile approach, with the development team working both remotely and in country to identify and solve key technical and cultural issues in close collaboration with the midwife end-users. This article describes this process and intermediate results. The application prototype was refined in two phases, with expanding numbers of end-users. Some of the key weaknesses identified in the system during the development cycles were user error when inserting and assembling cables and interacting with the 1-D ultrasound-recording interface, as well as unexpectedly poor bandwidth for data uploads in the central healthcare facility. Safety nets for these issues were developed and the resultant system was well accepted and highly utilized by the end-users. To evaluate the effectiveness of the system after full field deployment, data quality, and corruption over time, as well as general usage of the system and the volume of application support for end-users required by the in-country team was analyzed. Through iterative review of data quality and consistent use of user feedback, the volume and percentage of high quality recordings was increased monthly. Final analysis of the impact of the system on obstetrical referral volume and maternal and neonatal clinical outcomes is pending conclusion of the ongoing clinical trial.

Tyrosine phosphorylation of Kv1. 5 is upregulated in intrauterine growth retardation rats with exaggerated pulmonary hypertension

Intrauterine growth retardation (IUGR) is associated with the development of adult-onset diseases, including pulmonary hypertension. However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular dysfunction later in life is not fully understood. Here, we investigated the role of tyrosine phosphorylation of voltage-gated potassium channel 1.5 (Kv1.5) in this prenatal event that results in exaggerated adult vascular dysfunction. A rat model of chronic hypoxia (2 weeks of hypoxia at 12 weeks old) following IUGR was used to investigate the physiological and structural effect of intrauterine malnutrition on the pulmonary artery by evaluating pulmonary artery systolic pressure and vascular diameter in male rats. Kv1.5 expression and tyrosine phosphorylation in pulmonary artery smooth muscle cells (PASMCs) were determined. We found that IUGR increased mean pulmonary artery pressure and resulted in thicker pulmonary artery smooth muscle layer in 14-week-old rats after 2 weeks of hypoxia, while no difference was observed in normoxia groups. In the PASMCs of IUGR-hypoxia rats, Kv1.5 mRNA and protein expression decreased while that of tyrosine-phosphorylated Kv1.5 significantly increased. These results demonstrate that IUGR leads to exaggerated chronic hypoxia pulmonary arterial hypertension (CH-PAH) in association with decreased Kv1.5 expression in PASMCs. This phenomenon may be mediated by increased tyrosine phosphorylation of Kv1.5 in PASMCs and it provides new insight into the prevention and treatment of IUGR-related CH-PAH.

Monochorionic diamniotic twin pregnancy with selective IUGR type 2: fetoscopic and sonographic findings of ominous prognosis / Gestación gemelar monocorial complicada con RCIU selectiva tipo 2: hallazgos ecográficos y fetoscópicos de mal pronóstico

A woman with a monochorionic diamniotic twin pregnancy was referred to our Centre due to a discrepancy in size between the foetuses. She was 17 weeks' pregnant when the diagnosis of selective IUGR type 2 was made and the laser ablation of the placental anastomoses was performed. During the fetoscopy, we identified an arterio-venous anastomosis with bidirectional flow, which is atypical in this type of anastomoses (unidirectionals) and could represent a sign of ominous prognosis for the restricted twin.

Presentamos el caso de una gestante de 17 semanas con una gestación gemelar monocoriónica biamniótica complicada con RCIU selectivo tipo 2 que requirió, de acuerdo a criterios ecográficos, ablación quirúrgica láser de las anastomosis placentarias. Se identificó durante la fetoscopia una anastomosis arterio-venosa que mostraba flujo bidireccional lo cual es sumamente inusual en este tipo de anastomosis, no reportado antes en la literatura, constituyendo así un signo de mal pronóstico para el gemelo pequeño.

Impact of Continuous vs Bolus Feeding on Splanchnic Perfusion in Very Low Birth Weight Infants: A Randomized Trial.

OBJECTIVE: To detect changes in splanchnic perfusion and oxygenation induced by 2 different feeding regimens in infants with intrauterine growth restriction (IUGR) and those without IUGR. STUDY DESIGN: This was a randomized trial in 40 very low birth weight infants. When an enteral intake of 100 mL/kg/day was achieved, patients with IUGR and those without IUGR were randomized into 2 groups. Group A (n = 20) received a feed by bolus (in 10 minutes), then, after at least 3 hours, received the same amount of formula by continuous nutrition over 3 hours. Group B (n = 20) received a feed administered continuously over 3 hours, followed by a bolus administration (in 10 minutes) of the same amount of formula after at least 3 hours. On the day of randomization, intestinal and cerebral regional oximetry was measured via near-infrared spectroscopy and Doppler ultrasound (US) of the superior mesenteric artery was performed. Examinations were performed before the feed and at 30 minutes after the feed by bolus and before the feed, at 30 minutes after the start of the feed, and at 30 minutes after the end of the feed for the 3-hour continuous feed. RESULTS: Superior mesenteric artery Doppler US showed significantly higher perfusion values after the bolus feeds than after the continuous feeds. Near-infrared spectroscopy values remained stable before and after feeds. Infants with IUGR and those without IUGR showed the same perfusion and oxygenation patterns. CONCLUSION: According to our Doppler US results, bolus feeding is more effective than continuous feeding in increasing splanchnic perfusion. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01341236.

The fetal programming of food preferences: current clinical and experimental evidence.

Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. RESULTS: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

Clinical associations to abnormal umbilical cord length in Latin American newborns.

INTRODUCTION: Umbilical cord is vital to fetal development and its alterations are related to fetal and neonatal deaths and to late neurological complications. Abnormal cord length has been recognized as the most important cord feature leading to unfavorable outcomes. We aimed to examine the relationship between fetal abnormalities and the length of umbilical cord using the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas/Latin American Collaborative Study on Congenital Malformations) database. METHODS: Using ECLAMC case-control registries, we conducted an observational study on the relationship between umbilical cord length and clinical variables such as chromosomal abnormalities and neonatal malformations. RESULTS: Birth registries totaled 61820; of them 3411 had complete cord data. Abnormal length was found in 427, with 174 short (5.10%) cords and 253 long (7.41%) cords. No relation was found between abnormal cord length and gender, parity or parents' age. More abnormal length cords were found than reported in other series; unexpectedly, more long cords were observed in twin gestations. It was observed that among short cords (174), 105 were from newborns with some type of malformation and 69 with no malformation (OR = 2.92, CI (95%) 2.15-3.98, p = 0.0001); of the 253 long cords, 168 had malformation and only 85 did not (OR = 3.80, CI (95%) 2.91-4.96, p = 0.0001). CONCLUSIONS: Abnormal cord length is associated with fetal malformation. Further studies are needed to determine the clinical applicability of using this parameter in counseling during prenatal visits.