Buruli ulcer, tuberculosis and leprosy: Exploring the One Health dimensions of three most prevalent mycobacterial diseases: A narrative review.

ΟBJECTIVES: Although Buruli ulcer, tuberculosis, and leprosy are the three most common mycobacterial diseases, One Health dimensions of these infections remain poorly understood. This narrative review aims at exploring the scientific literature with respect to the presence of animal reservoir(s) and other environmental sources for the pathogens of these infections, their role in transmission to humans and the research on/practical implementation of One Health relevant control efforts. METHODS: The literature review was conducted using the online databases PubMed, Scopus, ProQuest and Google Scholar, reviewing articles that were written in English in the last 15 years. Grey literature, published by intergovernmental agencies, was also reviewed. RESULTS: For the pathogen of Buruli ulcer, evidence suggests possums as a possible animal reservoir and thus having an active role in disease transmission to humans. Cattle and some wildlife species are deemed as established animal reservoirs for tuberculosis pathogens, with a non-negligible proportion of infections in humans being of zoonotic origin. Armadillos constitute an established animal reservoir for leprosy pathogens with the transmission of the disease from armadillos to humans being deemed possible. Lentic environments, soil and other aquatic sources may represent further abiotic reservoirs for viable Buruli ulcer and leprosy pathogens infecting humans. Ongoing investigation and implementation of public health measures, targeting (sapro)zoonotic transmission can be found in all three diseases. CONCLUSION: Buruli ulcer, tuberculosis and leprosy exhibit important yet still poorly understood One Health aspects. Despite the microbiological affinity of the respective causative mycobacteria, considerable differences in their animal reservoirs, potential environmental sources and modes of zoonotic transmission are being observed. Whether these differences reflect actual variations between these diseases or rather knowledge gaps remains unclear. For improved disease control, further investigation of zoonotic aspects of all three diseases and formulation of One Health relevant interventions is urgently needed.

Active case finding of pulmonary TB in a European refugee camp: lessons learnt from Oinofyta hosting site in Greece.

OBJECTIVES: To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission. METHODS: Upon diagnosis of 3 TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5 mm). RESULTS: 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman. CONCLUSIONS: In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants.

Factors associated with relevant knowledge of intestinal schistosomiasis and intention to participate in treatment campaigns: a cross sectional survey among school children at Ijinga Island on Lake Victoria, North-Western Tanzania.

BACKGROUND: Annual Mass Drug Administration (MDA) using praziquantel targeting primary school children is the main control strategy against schistosomiasis in Tanzania. However, there are concerns about decreasing participation in mass drug administration among primary school children for unknown reasons. Therefore, the aim of this study was to identify factors related to relevant knowledge about schistosomiasis and the intention to participate in mass drug administration among primary school children in order to give recommendations for future projects. METHODS: A cross sectional, extended knowledge, attitudes and practices (KAP) survey was conducted among 356 primary school children aged 5-17 years in February-March 2016 using a pre-tested questionnaire. This survey was part of a baseline assessment for an integrated proof of concept study aiming towards schistosomiasis elimination on Ijinga Island. Outcomes of interest in logistic regression analysis were relevant knowledge and high intention to participate in treatment campaigns. Explanatory variables were sociodemographic information sources and elements aligned to Protection Motivation Theory (PMT). RESULTS: Only 17% of the children had relevant intestinal schistosomiasis related knowledge and very few of them knew any of the S. mansoni manifestations and complications. Factors associated with relevant schistosomiasis knowledge were previous diagnosis of schistosomiasis (aOR = 2.43, 95%CI: 1.1-5.6), having heard about schistosomiasis at school (aOR = 9.94, 95%CI: 5.0-19.7) and being enrolled in 6th or 7th grade (aOR = 3.94, 95%CI: 1.3-11.8). Only 40% of the children demonstrated high intention to participate in treatment campaigns. Factors associated with high intention to participate in MDA were previous diagnosis (aOR = 2.23, 95%CI: 1.1-4.7), perceived general risk of disease transmission by lake water (aOR = 1.79, 95%CI: 1.0-3.1), perceived own vulnerability of getting infected (aOR = 5.10, 95%CI: 2.1-12.6), perceived danger of the disease (aOR = 2.47, 95%CI: 1.3-4.8) and the perceived effectiveness of medicaments to cure the disease (aOR = 2.86, 95%CI: 1.4-5.7). CONCLUSIONS: The minority of the school children had high level of theoretical knowledge about schistosomiasis and a small proportion of the children demonstrated high intention to participate in mass drug administration. In general, practical knowledge on preventive measures such as taking anti-schistosomiasis drug during MDA need to be impacted in school children to increase their participation in the control program.

Factors associated with the delay of diagnosis of leprosy in north-eastern Colombia: a quantitative analysis.

OBJECTIVES: To determine the average time in months between the beginning of symptoms and the diagnostic confirmation of leprosy by the health system and to investigate factors associated with diagnostic delay. METHODS: A total of 249 patients older than 15 years diagnosed with leprosy between 2011 and 2015, in 20 endemic municipalities of north-eastern Colombia, provided informed consent and were interviewed face-to-face. Clinical histories from health centres or hospitals where study participants were treated for leprosy were also reviewed. RESULTS: The mean delay in diagnosis of leprosy was 33.5 months. About 14.9% of patients showed a visible deformity or damage (disability grade 2, DG2) at the time of diagnosis. In multivariable regression analysis, five or more consultancies required to confirm the diagnosis and not seeking care immediately after noticing first symptoms were associated with longer diagnostic delay. CONCLUSIONS: Our study found a significant delay in diagnosis of leprosy in north-eastern Colombia, which might explain the continuously high rate of DG2 among new cases being notified in the country. Both patient- and health system-related factors were associated with longer diagnostic delay. Interventions to increase awareness of disease among the general population and timely referral to a specialised health professional are urgently needed in our study setting.

Stature is inversely associated with self-reported diabetes in middle-aged Mexican women.

OBJECTIVE: To investigate whether stature is associated with two highly prevalent cardiom- etabolic disorders-diabetes mellitus (DM) and high blood pressure (HBP) -in middle-aged Mexican women. METHODS: We conducted a cross-sectional analysis of a sample of 93 481 middle-aged Mexican female teachers, all participating in the Mexican Teachers Cohort (MTC, or ESMaestras) study. We used a multivariable regression model to investigate the association of stature quintiles with the self-reported outcomes of DM and HBP. RESULTS: After adjusting for birth cohort, ethnicity, family history, birthweight, occupation of household's head during participant's childhood, menopausal status, and geographical region of birthplace, stature was inversely associated with DM, with the odds for DM being 9% higher in the lowest stature quintile when compared to the highest stature quintile. Stratification for location of residence resulted in confirmation of the above-mentioned findings only in partici- pants living in urban environments. CONCLUSIONS: We found an inverse association of stature with DM but not with HBP. Our data suggest that urban setting might be an important effect modifier of this association, which merits further investigation since it might provide valuable insights into the epidemiological transition occurring in developing countries.

OBJETIVO: Investigar si la estatura está asociada a dos trastornos cardiometabólicos ­ diabetes sacarina e hipertensión arterial­ muy prevalentes en las mujeres mexicanas de mediana edad. MÉTODOS: Realizamos un análisis transversal de una muestra de 93 481 maestras mexicanas de mediana edad que participaban en el Estudio de la Salud de las Maestras (ESMaestras). Utilizamos un modelo de regresión multivariante para investigar la relación entre los quintiles de estatura y los resultados autonotificados de diabetes sacarina e hipertensión arterial. RESULTADOS: Después de ajustar los datos en función de la cohorte de nacimiento, la etnicidad, los antecedentes familiares, el peso al nacer, la ocupación del jefe del hogar durante la niñez de la participante, el estado menopáusico y la zona geográfica del lugar de nacimiento, se observó una relación inversa entre la estatura y la diabetes sacarina, dado que las probabilidades de aparición de esta última fue un 9 % mayor en el quintil más bajo de estatura que en el quintil más alto. La estratificación en función de la residencia permitió confirmar los resultados mencionados solo respecto de aque- llas participantes que vivían en entornos urbanos. CONCLUSIONES: Encontramos una relación inversa entre la estatura y la diabetes saca- rina, pero no entre la estatura y la hipertensión arterial. Nuestros datos indican que el entorno urbano podría modificar considerablemente el efecto de esta relación, lo que amerita continuar con las investigaciones dado que podrían arrojar una luz valiosa sobre la transición epidemiológica en los países en desarrollo.

Vaccine value profile for Hookworm.

Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and remains one of the leading causes of mild to severe anemia in Low and Middle Income Countries (LMICs), particularly in pregnancy and children under 5. Despite repeated large scale Preventive Chemotherapy (PC) interventions since more than 3 decades, there is broad consensus among scholars that elimination targets set in the newly launched NTD roadmap will require additional tools and interventions. Development of a vaccine could constitute a promising expansion of the existing arsenal against hookworm. Therefore, we have evaluated the biological and implementation feasibility of the vaccine development as well as the added value of such a novel tool. Based on pipeline landscaping and the current knowledge on key biological aspects of the pathogen and its interactions with the host, we found biological feasibility of development of a hookworm vaccine to be moderate. Also, our analysis on manufacturing and regulatory issues as well as potential uptake yielded moderate implementation feasibility. Modelling studies suggest a that introduction of a vaccine in parallel with ongoing integrated interventions (PC, WASH, shoe campaigns), could substantially reduce burden of disease in a cost - saving mode. Finally a set of actions are recommended that might impact positively the likelihood of timely development and introduction of a hookworm vaccine.

Estimation of the morbidity and mortality of congenital Chagas disease: A systematic review and meta-analysis.

Chagas disease is caused by the parasite Trypanosoma cruzi which can be transmitted from mother to baby during pregnancy. There is no consensus on the proportion of infected infants with clinical signs of congenital Chagas disease (cCD). The objective of this systematic review is to determine the burden of cCD. Articles from journal inception to 2020 reporting morbidity and mortality associated with cCD were retrieved from academic search databases. Observational studies, randomized-control trials, and studies of babies diagnosed with cCD were included. Studies were excluded if they were case reports or series, without original data, case-control without cCD incidence estimates, and/or did not report number of participants. Two reviewers screened articles for inclusion. To determine pooled proportion of infants with cCD with clinical signs, individual clinical signs, and case-fatality, random effects meta-analysis was performed. We identified 4,531 records and reviewed 4,301, including 47 articles in the narrative summary and analysis. Twenty-eight percent of cCD infants showed clinical signs (95% confidence interval (CI) = 19.0%, 38.5%) and 2.2% of infants died (95% CI = 1.3%, 3.5%). The proportion of infected infants with hepatosplenomegaly was 12.5%, preterm birth 6.0%, low birth weight 5.8%, anemia 4.9%, and jaundice 4.7%. Although most studies did not include a comparison group of non-infected infants, the proportion of infants with cCD with clinical signs at birth are comparable to those with congenital toxoplasmosis (10.0%-30.0%) and congenital cytomegalovirus (10.0%-15.0%). We conclude that cCD burden appears significant, but more studies comparing infected mother-infant dyads to non-infected ones are needed to determine an association of this burden to cCD.

Knowledge, attitudes, behaviors, and serological status related to Chagas disease among Latin American migrants in Germany: A cross-sectional study in six German cities.

Background: Little is known about knowledge, attitudes and behaviors concerning Chagas disease (CD) among Latin American migrants in Germany to inform public health decision making. Methods: A cross-sectional, questionnaire-based study was conducted between March 2014 and October 2019 among Latin American migrants in six cities in Germany to obtain information on migration history, socioeconomic and insurance status, knowledge about CD, potential risk factors for Trypanosoma cruzi infection, and willingness to donate blood or organs. Results: 168 participants completed the questionnaire. The four countries with the highest proportion of participants contributing to the study population were Colombia, Mexico, Peru and Ecuador. Before migrating to Europe, the majority of the study population resided in an urban setting in houses made of stone or concrete, had higher academic education and was integrated into the German healthcare and healthcare insurance system. The majority of all study participants were also willing to donate blood and organs and a quarter of them had donated blood previously. However, many participants lacked basic knowledge about symptoms and modes of transmission of Chagas disease. One out of 56 serologic tests (1.8%) performed was positive. The seropositive female participant born in Argentina had a negative PCR test and no signs of cardiac or other organ involvement. Conclusions: The study population does not reflect the population structure at risk for T. cruzi infection in endemic countries. Most participants had a low risk profile for infection with T. cruzi. Although the sample size was small and sampling was not representative of all persons at risk in Germany, the seroprevalence found was similar to studies previously conducted in Europe. As no systematic screening for T. cruzi in Latin American blood and organ donors as well as in women of child-bearing age of Latin American origin is implemented in Germany, a risk of occasional transmission of T. cruzi remains.

Erratum: Psychosocial burden of neglected tropical diseases in eastern Colombia: an explorative qualitative study in persons affected by leprosy, cutaneous leishmaniasis and Chagas disease - ERRATUM.

[This corrects the article DOI: 10.1017/gmh.2021.18.].

Psychosocial burden of neglected tropical diseases in eastern Colombia: an explorative qualitative study in persons affected by leprosy, cutaneous leishmaniasis and Chagas disease.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases (NTDs) with a high psychosocial burden in Norte de Santander and Arauca in Colombia. This study provides insights into affected persons' feelings, perceptions and experiences to better understand the nature of this burden. METHODS: In 2018, 34 leprosy, CD and CL patients participated in four focus groups discussing the influence of the disease on mental well-being, social participation and stigma. Additionally, 13 leprosy patients participated in semi-structured interviews to further explore the health-related stigma related to this disease. Audio recordings were transcribed verbatim, and open coding was used to identify the most relevant categories and themes. RESULTS: Persons suffering from CD reported that their mental distress was mainly caused by impairments and stress related to the progressive and incurable nature of the disease. Persons affected by CL perceived the treatment for the disease as having the most impact on their psychosocial well-being. Persons affected by leprosy reported suffering most from anticipated and experienced stigma. CONCLUSIONS: The findings indicate that these diseases are likely to impose a significant psychosocial burden on patients in the studied regions, even though these vary per condition. Consistent data collection on the psychosocial burden and the sharing of knowledge of effective interventions can contribute to the holistic approach needed to win the fight against NTDs.

Measuring endemicity and burden of leprosy across countries and regions: A systematic review and Delphi survey.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level. METHODS: We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indicators, classification levels, and scoring methods to measure and classify endemicity and burden. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods. RESULTS: The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disability. For burden these include NCDR, MB cases, and prevalence. The classification levels 'high' and 'low' were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators. CONCLUSION: There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies.

Appraisal of a Contact Tracing Training Program for COVID-19 in Greece Focusing on Vulnerable Populations.

BACKGROUND: Contact tracing as an epidemiological strategy has repeatedly contributed to the containment of various past epidemics and succeeded in controlling the spread of disease in the community. Systematic training of contact tracers is crucial in ensuring the effectiveness of epidemic containment. METHODS: An intensive training course was offered to 216 health and other professionals who work with vulnerable population groups, such as Roma, refugees, and migrants in Greece, by the scientific team of the postgraduate programme "Global Health-Disaster Medicine" of the Medical School, National and Kapodistrian University of Athens, with the support of the Swiss embassy in Greece. The course was delivered online due to the pandemic restriction measures and was comprised of 16 h over 2 days. The course curriculum was adapted in Greek using, upon agreement, a similar training course to what was developed by the Johns Hopkins University Bloomberg School of Public Health. Evaluation of the course was conducted in order to determine the short term satisfaction from participating in this training course. RESULTS: A total of 70% of the course participants completed the evaluation questionnaires and all trainers gave feedback on the course. The training modules were ranked as extremely useful by the majority of the participants and over 50% of the participants specifically stated that the course content was directly related to their work with vulnerable groups. Content about the ethics of contact tracing and the effective communication skills presented were deemed most useful. CONCLUSION: The course was well organised and provided the required skills for effective contact tracing. Many course participants intend to use some components in their work with vulnerable populations groups. Contact tracing efforts work best in a systematic and coordinated way and the provision of systematic and organised training can greatly increase its effectiveness.

In the midst of the perfect storm: Swift public health actions needed in order to increase societal safety during the COVID-19 pandemic.

The phenomenal speed of COVID-19 has subjected the public health professionals worldwide to struggle to subdue the spread of the disease and its impact of the affected societies. The limited biomedical and epidemiological understanding of COVID-19 along with the lack of vaccines and therapeutics have led to the reception of draconian measures from the societal safety domain, limiting human interaction through social distancing. Grounded on the adopted approaches, interventions in sero-prevalence studies, mobilisation of the primary health care (PHC) sector, as well as target socially vulnerable groups should be taken into consideration by heath authorities.

Stigma, participation restriction and mental distress in patients affected by leprosy, cutaneous leishmaniasis and Chagas disease: a pilot study in two co-endemic regions of eastern Colombia.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases with a high psychosocial burden (PSB). These conditions are endemic in Norte de Santander and Arauca in Colombia, but data on the related PSB are scarce. Therefore, we assessed mental distress, participation restriction and stigma among CD, CL and leprosy patients. METHODS: In 2018, 305 leprosy, CD or CL patients were interviewed using a self-report questionnaire to assess mental distress, participation scale for participation restriction and explanatory model interview catalogue (EMIC) for stigma. Descriptive statistics and the significance of median score differences were compared. RESULTS: Fifty percent of CD patients and 49% of leprosy patients exhibited mental distress, percentages which were significantly higher than that of CL (26%). Twenty-seven percent of leprosy patients experienced participation restriction, which was lower for CL (6%) and CD (12%). Median EMIC scores were significantly higher for leprosy patients than for CD (27%) and CL (17%) patients. CONCLUSIONS: We found high levels of PSB among leprosy, CD and CL patients. Mental distress was highest among CD patients. Participation restriction and stigma were more prevalent in leprosy patients. Rural residence or lower educational status may impact PSB. Further investigation is needed to formulate evidence-based, holistic interventions.

Non-communicable diseases and tuberculosis: Anticipating the impending global storm.

The epidemiological transitions that have occurred in low and middle income countries (LMIC) during the past decades have led to an increased prevalence on non-communicable diseases (NCDs) in these countries, where the burden of infectious diseases (IDs), especially tuberculosis (TB), remains high. Although the true dimensions of this comorbidity have not yet been fully understood, there is a growing amount of data, over the last 10 years, that suggest a clear association between NCDs and TB. In particular, there is a continuously increasing body of evidence that diabetes mellitus, chronic respiratory conditions, tobacco use, mental health illnesses and chronic kidney disease increase TB morbidity and mortality and vice versa. This bidirectional negative association between diseases may jeopardise the achievement of the Sustainable Development Goals (SDGs) specific TB targets, thus underlying the importance of integrated public health responses towards both epidemics. Population as well as individual based approaches are required, along with both strategic and operation integration on a global scale. This year's United Nations High Level Meetings (ΗLMs) presented a rare opportunity for the political foundations of the TB and NCD responses to be dug together, thus creating a potential breakthrough in the global response to both epidemics.

Time to Rethink Refugee and Migrant Health in Europe: Moving from Emergency Response to Integrated and Individualized Health Care Provision for Migrants and Refugees.

In the last three years, the European Union (EU) is being confronted with the most significant influx of migrants and refugees since World War II. Although the dimensions of this influx-taking the global scale into account-might be regarded as modest, the institutional response to that phenomenon so far has been suboptimal, including the health sector. While inherent challenges of refugee and migrant (R&M) health are well established, it seems that the EU health response oversees, to a large extend, these aspects. A whole range of emergency-driven health measures have been implemented throughout Europe, yet they are failing to address adequately the changing health needs and specific vulnerabilities of the target population. With the gradual containment of the migratory and refugee waves, three years after the outbreak of the so-called 'refugee crisis', we are, more than ever, in need of a sustainable and comprehensive health approach that is aimed at the integration of all of migrants and refugees-that is, both the new and old population groups that are already residing in Europe-in the respective national health systems.

Intrauterine growth restriction and circulating neurotrophin levels at term.

BACKGROUND: Intrauterine growth restricted (IUGR) fetuses are those with estimated weight <10th customized centile, displaying signs of chronic malnutrition and hypoxia leading to brain sparing effect. Neurotrophins, [Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), Neurotrophin-4 (NT-4)] are important for pre- and post-natal brain development. AIMS: To investigate circulating NGF, BDNF, NT-3 and NT-4 levels in IUGR and appropriate for gestational age (AGA) fullterm fetuses and neonates (day-1 [N1] and day-4 [N4]) and in their mothers. STUDY DESIGN: Prospective case control study. SUBJECTS: 60 mothers and their single 30 IUGR and 30 AGA fullterm fetuses and neonates. OUTCOME MEASURES: Determination, by enzyme immunoassays, of NGF, BDNF, NT-3 and NT-4 plasma levels. RESULTS: No statistically significant differences existed between IUGR and AGA maternal, fetal and neonatal levels of BDNF, NT-3 and NT-4. NGF was significantly higher in AGA than IUGR maternal (p=0.007), fetal (p=0.01), neonatal day 1 (p=0.043) and 4 (p=0.003) plasma, and positively correlated with the infants' centiles and birthweights. IUGR and AGA maternal neurotrophins were higher than the respective fetal and neonatal ones and no correlation with gender or delivery mode in both groups was observed. CONCLUSIONS: In the perinatal period, circulating levels of BDNF, NT-3 and NT-4 do not differ in IUGR and AGA pregnancies, in contrast to NGF levels, which are higher in the AGA group. NGF is the only neurotrophin correlating with customized centiles and birthweights of the infants. Neurotrophin concentrations are higher in maternal plasma and do not depend on gender.

Insulin-like growth factor (IGF)-I and insulin in normal and growth-restricted mother/infant pairs.

Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We investigated perinatal changes of both factors in 40 mothers and their 20 appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and N1, but not N4, IGF-I levels were increased in AGA (P < .001 and P = .037, resp.). N1 insulin levels were lower in IUGR (P = .048). Maternal, fetal, and N1 IGF-I, and fetal insulin levels positively correlated with customized centiles (r = .374, P = .035, r = .608, P < .001, r = .485, P = .006, and r = .654, P = .021, resp.). Female infants presented elevated fetal and N4 IGF-I levels (P = .023 and P = .016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I levels, and fetal insulin levels with customized centiles underline implication of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I levels. Higher IGF-I levels are documented in females.

Perinatal plasma monocyte chemotactic protein-1 concentrations in intrauterine growth restriction.

Monocyte-chemotactic-protein-1 (MCP-1) plays vital roles in immune response, angiogenesis, and pregnancy outcome. We investigated plasma MCP-1 concentrations in 40 mothers and their 20 intrauterine-growth-restricted (IUGR) and 20 appropriate-for-gestational-age (AGA) fetuses and neonates on postnatal days 1 (N1) and 4 (N4). Maternal and fetal MCP-1 concentrations were decreased (P<001 and P = .018, resp.), whereas N1 MCP-1 concentrations were elevated in IUGR group (P = .012). In both groups, fetal MCP-1 concentrations were lower compared to N1 and N4 ones (P = .045, P = .012, resp., for AGA, P< .001 in each case for IUGR). Reduced maternal and fetal MCP-1 concentrations in IUGR may reflect failure of trophoblast invasion, suggesting that down-regulation of MCP-1 may be involved in the pathogenesis of IUGR. Increased MCP-1 concentrations in IUGR neonates and higher postnatal ones in all infants may be attributed to gradual initiation of ex utero angiogenesis, which is possibly enhanced in IUGR.