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Introduction: Headache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Grouphas prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. Development: This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. Conclusions: We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients., Introducción: La cefalea es uno de los motivos de consulta más comunes en neurología, siendo más frecuente durante la edad reproductiva. Por ello, es habitual encontrar en nuestras consultas pacientes embarazadas o en periodo de lactancia con dicha queja. Es importante conocer las opciones farmacológicas más seguras, cuáles no se deben emplear, así como cuándo sospechar cefaleas secundarias. Por este motivo, el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología ha elaborado una guía con las recomendaciones consensuadas acerca de los algoritmos diagnósticos y terapéuticos que se deben emplear durante el embarazo y la lactancia

Background Fetal growth restriction (FGR) affects 7–10% of all pregnancies resulting in a higher risk of perinatal morbidity and mortality, long-term disabilities, and cognitive impairment. Due to its multifactorial etiology, changes in maternal lifestyle, including suboptimal maternal diet and stress, have increasingly been associated with its prevalence. We present a protocol for the Improving Mothers for a better PrenAtal Care Trial Barcelona (IMPACT BCN), which evaluates two different maternal lifestyle strategies (improved nutrition by promoting Mediterranean diet and stress reduction program based on mindfulness techniques) on perinatal outcomes. The primary objective is to reduce the prevalence of FGR. Secondary aims are to reduce adverse perinatal outcomes and to improve neurodevelopment and cardiovascular profile in children at 2 years of age. Methods A randomized parallel, open-blind, single-center trial following a 1:1:1 ratio will select and randomize high-risk singleton pregnancies for FGR (N=1218), according to the criteria of the Royal College of Obstetricians and Gynaecologists (19.0–23.6 weeks’ gestation), into three arms: Mediterranean diet, mindfulness-based stress reduction program, and usual care without any intervention. Compliance to the interventions will be randomly tested in 30% of participants with specific biomarkers. Maternal socio-demographic, clinical data, biological samples, and lifestyle questionnaires will be collected at enrollment and at the end of the interventions (34.0–36.6 weeks’ gestation), together with a fetoplacental ultrasound and magnetic resonance. Fetoplacental biological samples and perinatal outcomes will be recorded at delivery. Postnatal follow-up is planned up to 2 years of corrected age including neurodevelopmental tests and cardiovascular assessment. Intention-to-treat and population per-protocol analysis will be performed. Discussion This is the first randomized study evaluating the impact of maternal lifestyle interventions during pregnancy on perinatal outcomes. The maternal lifestyle interventions (Mediterranean diet and mindfulness-based stress reduction program) are supported by scientific evidence, and their compliance will be evaluated with several biomarkers. Trial registration ClinicalTrials.govNCT03166332. Registered on April 19, 2017

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR.

Women living with HIV (WLH) lack evidence-based information about reproductive options while managing pressures from family, clinicians, and communities to give up the idea of having children. As the reproduction intentions of WLH are not well understood, stigmatizing behaviors force them to hide their disease to avoid rejection by their family, partner, and social networks. Compliance with social norms, fear of stigma, and discrimination influence their experience. Current research is individual qualitative studies lacking the synthesis perspective necessary to guide intervention development. The purpose of this study was to synthesize the evidence to explain the reproductive decision-making process for WLH in developed countries.A systematic review with qualitative research synthesis was conducted through searches in 10 electronic databases (CINAHL, EMBASE, MEDLINE, Scopus, Social Science Citation Index, Web of Science, Google Scholar, Cuidatge, Cuiden Enfispo, and SciELO). Studies published in journals from 1995 to 2019 with qualitative data about reproductive decision-making among WLH in developed countries were eligible for inclusion. Developed country was operationalized by membership in the OECD for comparative conditions of social wellbeing and economic stability. The CASP and JBI checklists for qualitative research were used to assess study quality and methodological integrity. Thematic analysis and qualitative meta-summary techniques were used for the synthesis.Twenty studies from 12 developed countries were included in the synthesis. Findings were organized into 3 meta-themes from 15 themes and 45 subthemes, including: (1) Shattered identity, (2) Barriers, inequities, and misinformation, (3) Coping, resiliency, and support. Reproductive decision-making was perceived as a complex process influenced by facilitators and barriers. The facilitators helped WLH cope with their new situation to become more resilient, while the barriers made their situation more difficult to manage.WLH encounter reproductive decision-making with knowledge deficits and limited social support. An integrated approach to holistic care with comprehensive multidisciplinary counseling is needed to support WLH. Clinicians could benefit from professional development to learn how to be authentically present for WLH, including engaging in conversations, demonstrating compassion, and understanding situations. Evidence-based clinical practice guidelines need to be tailored for the family planning and sexual health needs of WLH.ANTECEDENTES: Las mujeres que viven con el VIH (MVV) carecen de información basada en evidencias sobre las opciones reproductivas mientras son presionadas por la familia, los profesionales de la salud y los miembros de la comunidad para renunciar a la idea de tener hijos. Como las intenciones reproductivas de las MVV no son comprendidas, las conductas estigmatizantes las obligan a ocultar su enfermedad para evitar el rechazo de su familia, pareja y grupos sociales. El cumplimiento de las normas sociales, el miedo al estigma y la discriminación influyen en su experiencia. La presente investigación está compuesta por estudios cualitativos que de forma individual carecen de la perspectiva de síntesis necesaria para guiar el desarrollo de las intervenciones. El propósito de este estudio fue sintetizar la evidencia para explicar el proceso de toma de decisiones reproductivas para las MVV en los países desarrollados. MéTODOS: Se realizó una revisión sistemática con síntesis de investigación cualitativa mediante búsquedas en 10 bases de datos electrónicas (CINAHL, EMBASE, MEDLINE, Scopus, Social Science Citation Index, Web of Science, Google Scholar, Cuidatge, Cuiden Enfispo y SciELO). Los estudios publicados en revistas de entre 1995 y 2019 que contuvieran datos cualitativos sobre la toma de decisiones reproductivas entre las MVV en países desarrollados fueron elegibles para su inclusión. Se consideraron países desarrollados aquellos que pertenecieran a la OCDE con el objetivo de comparar condiciones de bienestar social y estabilidad económica. Las listas de verificación CASP y JBI para la investigación cualitativa se utilizaron para evaluar la calidad del estudio y la integridad metodológica. Para la síntesis se utilizaron técnicas de análisis temático y metanálisis cualitativo.En la síntesis se incluyeron veinte estudios de 12 países desarrollados. Los hallazgos se organizaron en 3 metatemas de 15 temas y 45 subtemas, incluyendo: (1) Identidad fragmentada, (2) Barreras, inequidades y desinformación, (3) Afrontamiento, resiliencia y apoyo. La toma de decisiones reproductivas se percibió como un proceso complejo influenciado por factores facilitadores y barrera. Los facilitadores ayudaron a las MVV a afrontar su nueva realidad para volverse más resilientes, mientras que las barreras hicieron que su situación fuera más difícil de manejar. CONCLUSIóN: Las MVV enfrentan la toma de decisiones reproductivas con déficits de conocimiento y apoyo social limitado. Es necesario adoptar un enfoque holístico de atención integral con asesoramiento multidisciplinario para acompañar a las MVV. Los clínicos podrían beneficiarse del desarrollo profesional para aprender a estar verdaderamente presentes para las MVV, participando en reflexiones, demostrando compasión y comprendiendo sus situaciones. Las guías de práctica clínica basadas en la evidencia deben adaptarse a las necesidades de planificación familiar y salud sexual y reproductiva de las MVV. Plain Language Summary Women living with HIV can become pregnant and deliver a healthy baby due to advances in medicine. Being a mother is an important role that gives meaning to life for most women. For women living with HIV thinking about having a baby is difficult because HIV complicates many areas of daily living. When women living with HIV try to speak with physicians and nurses about having a baby, they often do not feel supported and report feeling stigmatized. This review of the scientific literature summarizes the experiences of women living with HIV in developed countries as they considered having a baby. Ten electronic databases were searched for studies published between 1995 and 2019 reporting interviews with women living with HIV about becoming pregnant and having a baby. From the 4519 articles identified, 20 were included for review with 1395 participants from 12 developed countries. After abstracting and analyzing the interviews, three themes were developed to summarize the process described by women living with HIV as they considered pregnancy and the possibility of having a baby, including: (1) Shattered identity, (2) Barriers, inequities, and misinformation, and (3) Coping, resiliency, and support. When women living with HIV consider having a baby, they need to feel comfortable and safe speaking with physicians and nurses about family planning. They also need more support from their partner, as well as family and friends. Strategies need to be implemented to improve the family planning process for women living with HIV, including education health care providers about speaking to women about pregnancy and having a healthy baby.

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of

A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother. Several factors that influenced the success of the pregnancy in this case were analyzed. Favorable factors included: triple positive breast cancer [positive hormone receptors and positive human epidermal growth factor receptor 2], which is more hormosensitive and chemosensitive; absence of metastasis; correct endometrium preparation; and the patient's optimistic attitude and strict health habits. In contrast, the factors against success were: breast cancer; adjuvant breast cancer therapy gonadotoxicity; the age of the patient (> 40-year-old); endometriosis; ovarian cyst; hydrosalpinx; submucosal fibroids and the respective associated surgery done for the above-mentioned pathology (all resolved prior to the embryo transfer); and a low quantity of ovules (low ovarian reserve) after ovarian stimulation. This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies, who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding.

Background: In recent years, higher than the recommended rate of oxytocin use has been observed among low-risk women. This study examines the relationship between oxytocin administration and birth outcomes in women and neonates. Methods: A retrospective analysis of birth and neonatal outcomes for women who received oxytocin versus those who did not. The sample included 322 women with a low-risk pregnancy. Results: Oxytocin administration was associated with cesarean section (aOR 4.81, 95% CI: 1.80–12.81), instrumental birth (aOR 3.34, 95% CI: 1.45–7.67), episiotomy (aOR 3.79, 95% CI: 2.20–6.52) and length of the second stage (aOR 00:18, 95% CI: 00:04–00:31). In neonatal outcomes, oxytocin in labor was associated with umbilical artery pH ≤ 7.20 (OR 3.29, 95% CI: 1.33–8.14). Admission to neonatal intensive care unit (OR 0.56, 95% CI: 0.22–1.42), neonatal resuscitation (OR 1.04, 95% CI: 0.22–1.42), and Apgar score &lt, 7 (OR 0.48, 95% CI: 0.17–1.33) were not associated with oxytocin administration during labor. Conclusions: Oxytocin administration during labor for low-risk women may lead to worse birth outcomes with an increased risk of instrumental birth and cesarean, episiotomy and the use of epidural analgesia for pain relief. Neonatal results may be also worse with an increased proportion of neonates displaying an umbilical arterial pH ≤ 7.20.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. Methods Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. Discussion There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population, The study has been awarded with a Spanish Government grant (Instituto de Salud Carlos III: COV20/00188). It covers the expenses for transporting, processing and analyzing samples, database creation and maintenance, and hiring support staff

Artículo con numerosos autores. Sólo destacamos el primero. el de la UAM y el Grupo colectivo, Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13–3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms, This project was supported by public funds obtained in competitive calls: Grant COV20/00021 (EUR 43,000 from the Instituto de Salud Carlos III—Spanish Ministry of Health and co-financed with Fondo Europeo de Desarrollo Regional (FEDER) funds. Dr Cruz-Lemini is supported by a Juan Rodés contract JR19/00047, Instituto de Salud Carlos III—Spanish Ministry of Health

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign., This research was supported by public funds obtained in competitive calls: Grant COV20/ 00021 from the Instituto de Salud Carlos III-Spanish Ministry of Health, and co-financed with Fondo Europeo de Desarrollo Regional (FEDER) funds

The objective of this study was to explore what motivates pregnant and breastfeeding women to make changes in their diet, specifically to examine how their perceptions regarding diet facilitate or act as obstacles to introducing healthy eating habits. For the optimal development of the mother, the fetus, or breastfeeding baby, it is important to avoid foods containing substances, such as persistent toxic substances (PTSs), that are harmful to health during pregnancy and after the baby&rsquo, s birth. This study used a qualitative research methodology, based on semi-structured individual interviews, food diaries, free lists, and focus groups with 111 pregnant and breastfeeding women in Spain. This approach was followed by a systematic and exhaustive exploitation of the qualitative data obtained, following the methodological principles of grounded theory. From the study results, we conclude that the motivation for a change in diet to avoid PTSs is based on the desire to promote good health, beliefs about the importance of having a varied diet, and the avoidance of potential risks. The main obstacles to change can be attributed to inadequate information, contradictory discourses, and socioeconomic difficulties.

Obesity in pregnancy has been directly associated with an increased risk of almost all pregnancy complications such as gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM), and premature delivery. Thereby, according to current evidence available, life-style interventions to prevent pre-pregnancy overweight and obesity in women of fertile age are necessary to reduce the negative impact of obesity on mother and child health. Unhealthy dietary patterns, together with the increased consumption of processed foods rich in simple sugar and sweeteners are some of the responsible, among others, for the increase in obesity rates during the last years. Nevertheless, how its consumption can affect pregnancy outcomes and long-term children’s health is still uncertain. This review aims to collate the available evidence about the consequences of unhealthy dietary patterns and sugary products consumption, including sweeteners, during pregnancy for obesity in childhood and mid-childhood. High simple sugar intake during gestation may contribute to an excessive gestational weight gain (GWG) as well as to develop other pregnancy complications such as GDM, preeclampsia and preterm birth. The heterogeneity of study populations, sample size, different approaches to measure GWG, GMD, preeclampsia, and birth weight, among other conditions, might explain the divergences observed among studies. Therefore, large, well-designed intervention-controlled trials with biological biomarkers to ensure dietary adherence are necessary to evaluate the effectiveness of lifestyle interventions in order to provide effective nutritional advice.

Background: In Europe, the majority of healthy women give birth at conventional obstetric units with the assistance of registered midwives. This study examines the relationships between the intrapartum transfer of care (TOC) from midwife to obstetrician-led maternity care, obstetric unit size (OUS) with different degrees of midwifery autonomy, intrapartum interventions and birth outcomes. Methods: A prospective, multicentre, cross-sectional study promoted by the COST Action IS1405 was carried out at eight public hospitals in Spain and Ireland between 2016&ndash, 2019. The primary outcome was TOC. The secondary outcomes included type of onset of labour, oxytocin stimulation, epidural analgesia, type of birth, episiotomy/perineal injury, postpartum haemorrhage, early initiation of breastfeeding and early skin-to-skin contact. A logistic regression was performed to ascertain the effects of studied co-variables on the likelihood that participants had a TOC, Results: Out of a total of 2,126 low-risk women, those whose intrapartum care was initiated by a midwife (1772) were selected. There were statistically significant differences between TOC and OUS (S1 = 29.0%, S2 = 44.0%, S3 = 52.9%, S4 = 30.2%, p &lt, 0.001). Statistically differences between OUS and onset of labour, oxytocin stimulation, type of birth and episiotomy or perineal injury were observed (p = 0.009, p &lt, 0.001, p &lt, 0.001 respectively), Conclusions: Findings suggest that the model of care and OUS have a significant effect on the prevalence of intrapartum TOC and the birth outcomes. Future research should examine how models of care differ as a function of the OUS in a hospital, as well as the cost-effectiveness for the health care system.

Background: Despite the fact that tobacco use during pregnancy produces adverse perinatal effects, some women continue to smoke. Health literacy (HL) is essential for health outcomes in adults. However, little is known about HL in pregnant women or postpartum women. The study aimed to analyse the relationship between the degree of HL of women during the early puerperium and tobacco use during pregnancy. Methods: A multicentre, descriptive, cross-sectional study was carried out with women in the early puerperium in a region of eastern Spain, between November 2017 and May 2018. Their HL level was obtained using the Newest Vital Sign (NVS) tool. Multivariate logistic models were adjusted to estimate the magnitude of association with tobacco use in pregnancy. Odds ratios (OR) were estimated with a 95% confidence interval. Results: 193 were included in the total. 29.5% (57) of pregnant women smoked tobacco during pregnancy, with a smoking cessation rate of 70.1% (40) while pregnant. 42.0% (81) of pregnant women had inadequate or limited HL. A low level of HL was strongly associated with tobacco use, adjusted by catchment area and age of first pregnancy (LRT p &lt, 0.001, ROC curve = 0.71, 95% CI: 0.64&ndash, 0.79). Conclusion: A low HL is associated with tobacco consumption during pregnancy. Whether low HL reflects the wide constellation of already-known socioeconomic, political and commercial determinants of tobacco use, or whether incorporating HL support interventions strengthens tobacco cessation activities in pregnancy, warrants further research. Still, it should be considered as essential to understanding the health disparities related to its consumption.

Background: Prenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9-12 years. Method: Data came from 518 mother-child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9-12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and cortical surface area, and diffusion tensor imaging was used to measure white matter microstructure through fractional anisotropy (FA) and mean diffusivity (MD). Linear regression models were fit for the averaged prenatal exposure across pregnancy. Results: DM and DE metabolite concentrations were not associated with brain volumes, cortical thickness, and cortical surface area. However, a 10-fold increase in averaged DM metabolite concentrations across pregnancy was associated with lower FA (B = -1.00, 95%CI = -1.80, -0.20) and higher MD (B = 0.13, 95%CI = 0.04, 0.21). Similar associations were observed for DE concentrations. Conclusions: This study provides the first evidence that OP pesticides may alter normal white matter microstructure in children, which could have consequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area. This research received financial support from the intramural research program of the National Institute of Environmental Health Sciences, National Institutes of Health (Grant# HHSN273201500003C). Neuroimaging was supported by the ZonMw TOP project no. 91211021. Henning Tiemeier was supported by a grant of the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development, and NWO/ ZonMW grant 016.VICI.170.200). Mònica Guxens is funded by a Miguel Servet fellowship (MS13/00054, CPII18/00018) awarded by the Spanish Institute of Health Carlos III. Monica Guxens acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Programme. Dr. Hanan El Marroun was supported by Stichting Volksbond Rotterdam, the Dutch Brain Foundation (De Hersenstichting, project number GH2016.2.01) and the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 733206 LifeCycle)

Key Points Question Is fish consumption during pregnancy associated with benefits for the metabolic health of children? Findings In this cohort study of 805 mothers and their singleton offspring, moderate fish consumption during pregnancy was associated with the downregulation of inflammation and improvements in the metabolic profile of children; high mercury exposure during pregnancy had the opposite associations. Meaning The results of this study suggest that fish consumption consistent with current recommendations during pregnancy was associated with improvements in the metabolic health of children., Importance The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown. Objective To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children. Design, Setting, and Participants This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019. Exposures Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples. Main Outcomes and Measures An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, −4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children. Results The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = −0.96; 95% CI, −1.49 to −0.42) compared with low fish consumption (, This cohort study used data from the Human Early Life Exposome (HELIX) project, a collaboration of 5 European birth cohort studies, to examine the associations of maternal fish consumption and mercury exposure during pregnancy with metabolic health and inflammatory biomarkers in children.

Probiotics have shown potential for their use in early life. This study aimed to investigate whether the administration of Lactobacillus fermentum CECT5716 during pregnancy and lactation periods impacts maternal and offspring plasma lipid profile, immune system and microbiota. Rats were supplemented with the probiotic during gestation and two weeks of lactation. After supplementation, although the microbiota composition was not affected, the probiotic strain was detected in all cecal contents of dams and in some of their pups. Dams showed reduced proportion of T cytotoxic cells in the mesenteric lymph nodes, modulation of intestinal cytokines (IL-10 and IL-12) and changes in plasma fatty acids (20:0, 22:0, 20:5 n-3, and 18:3 n-6). Pups showed changes in immunoglobulins (intestinal IgA and plasmatic IgG2a and IgG2c) and fatty acid profile (17:0, 22:0, and 18:2 n-6). Overall, Lactobacillus fermentum CECT5716 supplementation contributed to beneficially modulating the immune system of the mother and its offspring.

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels

The increasing use of illegal drugs by pregnant women causes a public health concern because it is associated with health risks for mothers and their developing children. One of such drugs is MDMA (3,4-methylenedioxymethamphetamine) or ecstasy due to its high consumption in relevant age and sex groups and its adverse effects on human and rodent developing brains. To Journal Pre-proof 2 thoroughly review the current knowledge on the developmentally neurotoxic potential of MDMA we systematically collected and summarized articles investigating developmental neurotoxicity (DNT) of MDMA in humans and animals in in vivo and in vitro. In addition, we summarized the findings in a putative adverse outcome pathway (AOP). From an initial 299 articles retrieved from the bibliographic databases Web of Science, PubMed and DART, we selected 39 articles according to inclusion/exclusion criteria for data collection after title/abstract and full text screening. Of these 3 where epidemiological studies, 34 where in vivo studies in mice and rats and 2 were in vitro studies. The three epidemiological studies reported from the same longitudinal study and suggested that MDMA exposure during pregnancy impairs neuromotor function in infants. In rat, postnatal exposure towards MDMA also caused locomotor deficits as well as impaired spatial learning that might be associated with decreased serotonin levels in the hippocampus. In vitro MDMA caused cytotoxicity at high concentrations and effects on the serotonergic and neuritogenic alterations at lower concentrations which are in line with some of the in vivo alterations observed. Considering the adverse outcomes of developmental MDMA described in humans and in rodents we summarized the first putative AOP on developmental compound exposure leading to impaired neuromotor function in children. For generation of this AOP, MDMA exposure was taken as a model compound. In addition, we hypothesized a second AOP involving developmental disturbance of the dopaminergic system. However, further in vitro mechanistic studies are needed to understand the molecular initiating event(s) (MIE) triggering the downstream cascades and obtain consistent evidences causally linking the adverse outcome to effects at the cellular, organ and organism level.

The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards. This holistic concept of exposure provides a new framework to advance the understanding of complex and multifactorial diseases. Prospective pregnancy and birth cohort studies provide a unique opportunity for exposome research as they are able to capture, from prenatal life onwards, both the external (including lifestyle, chemical, social and wider community-level exposures) and the internal (including inflammation, metabolism, epigenetics, and gut microbiota) domains of the exposome. In this paper, we describe the steps required for applying an exposome approach, describe the main strengths and limitations of different statistical approaches and discuss their challenges, with the aim to provide guidance for methodological choices in the analysis of exposome data in birth cohort studies. An exposome approach implies selecting, pre-processing, describing and analyzing a large set of exposures. Several statistical methods are currently available to assess exposome-health associations, which differ in terms of research question that can be answered, of balance between sensitivity and false discovery proportion, and between computational complexity and simplicity (parsimony). Assessing the association between many exposures and health still raises many exposure assessment issues and statistical challenges. The exposome favors a holistic approach of environmental influences on health, which is likely to allow a more complete understanding of disease etiology. This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement 733206 (LifeCycle Project) and 874583 (ATHLETE Project).

Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through di erent mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding., This research was funded by the PN I+D+I 2008–2011 (Spain), ISCIII- Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF), RETICS Maternal and Child Health and Development Network, SAMID Network, Ref. RD16/0022/0015. Anna Parra-Llorca acknowledges Rio Hortega grant CM18/00165 from the Instituto de Investigación en Salud Carlos III (Ministry of Science, Universities and Innovation; Kingdom of Spain); Talía Sainz is funded by The Instituto de Salud Carlos III- Spanish Ministry of Science and Innovation cofounded by FEDER (EU). (Grant nº JR16/00021); Cristina Calvo is a member of the IdiPAZ Research Institute, Madrid. Spain. Translational Research Network for Pediatric Infectious Diseases (RITIP), Madrid, Spain. TEDDY Network Member (European Network of Excellence for Pediatric Clinical Research, Bari, Italy)

Background: For the past two decades, studies have investigated the relationship between periodontal disease and adverse pregnancy outcomes such as pre-eclampsia, preterm birth, low birth weight and preterm premature rupture of membranes. Objectives: To determine the prevalence of periodontal disease and associated adverse pregnancy outcomes among women delivering at the Kilimanjaro Christian Medical Centre (KCMC). Methods: This cross-sectional study was based on the use of patients’ files, clinical examinations and oral interviews with mothers who delivered at the KCMC. Pregnant women with singleton babies (N=1117) who delivered at the KCMC were recruited for the study. Intra-oral examination was performed within five days of birth. The Community Periodontal Index was used to assess periodontal disease Results: The prevalence of periodontal disease was 14.2%. Periodontal disease was significantly associated with higher odds of pre-eclampsia [adjusted Odds Ratio 95% Confidence Interval (aOR=4.12;95%CI:2.20-7.90)], low birth weight (aOR=2.41;95%CI:1.34-4.33) and preterm birth (aOR=2.32;95%CI:1.33-4.27). There was no significant association between periodontal disease and preterm premature rupture of membranes (aORs 1.83;95%CI:0.75-4.21) and eclampsia (3.71;95%CI:0.80-17.13). Conclusion: Maternal periodontal disease is a potential independent risk indicator for pre-eclampsia, low birth weight, and preterm birth. Periodontal assessment and therapy should form part of the preventive antenatal care provided to women in developing countries. Keywords: Preterm birth; low birth weight; pre-eclampsia; eclampsia; preterm premature rupture of membranes; periodontal disease; periodontitis; cross-sectional studies.

Background: Prenatal and postnatal exposure to air pollution has been linked to cognitive impairment in children, but very few studies have assessed its association with attentional function. Objectives: To evaluate the association between prenatal and postnatal exposure to nitrogen dioxide (NO2) and attentional function in children at 4–5 years of age. Methods: We used data from four regions of the Spanish INMA—Environment and Childhood—Project, a population-based birth cohort. Using land-use regression models (LUR), we estimated prenatal and postnatal NO2 levels in all of these regions at the participants' residential addresses. We assessed attentional function using the Kiddie-Conners Continuous Performance Test (K-CPT). We combined the region-specific adjusted effect estimates using random-effects meta-analysis. Results: We included 1298 children with complete data. Prenatal exposure to NO2 was associated with an impaired standard error of the hit reaction time (HRT(SE)) (increase of 1.12 ms [95% CI; 0.22 a 2.02] per 10 μg/m3 increase in prenatal NO2) and increased omission errors (6% [95% CI; 1.01 to 1.11] per 10 μg/m3 increase in prenatal NO2). Postnatal exposure to NO2 resulted in a similar but borderline significant increase of omission errors (5% [95% CI; =0.99 to 1.11] per 10 μg/m3 increase in postnatal NO2). These associations did not vary markedly between regions, and were mainly observed in girls. Commission errors and lower detectability were associated with prenatal and postnatal exposure to NO2 only in some regions. Conclusions: This study indicates that higher exposure to ambient NO2, mainly during pregnancy and to a lesser extent postnatally, is associated with impaired attentional function in children at 4–5 years of age., This study was funded by grants from the Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041 and PI031615; PI041931; PI041112; PI041436; PI041509; PI042018; PI051079; PI051052; PI060867; PI061213; PI070314; CP1100178; PI081151 incl. FEDER funds; PS0900090 incl. FEDER funds; PI0902311 incl. FEDER funds; PI0902647 incl. FEDER funds; PI1102591 incl. FEDER funds; PI1102038 incl. FEDER funds; PI131944 incl. FEDER funds; PI132032 incl. FEDER funds; PI1302429 incl. FEDER funds; PI1302187 incl. FEDER funds; PI140891 incl. FEDER funds; PI141687 incl. FEDER funds and MS13/00054), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Department of Health of the Basque Government (2005111093, 2009111069 and 2013111089), the Provincial Government of Gipuzkoa (DFG06/002 and DFG08/001), Convenios anuales con los ayuntamientos de la zona del estudio (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain), from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), from the European Research Council under the ERC Grant Agreement number ERC-AdG 2010 GA#268479 – the BREATHE project, from the Conselleria de Sanitat of Generalitat Valenciana (AP212/11, 002/008, 012/009, 013/2009, 014/009, 015/008, 016/009, 021/007, 021/008, 023/008 and 024/007) and from Obra Social Cajastur/Fundación Liberbank and Universidad de Oviedo. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological development, but it is unclear whether intrauterine or confounding factors drive this association.MethodsWe assessed whether maternal pre-pregnancy obesity was associated with neuropsychological development in 1,827 Spanish children. At 5 years, cognitive and psychomotor development was assessed using McCarthy Scales of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test. Models were adjusted for sociodemographic factors and maternal intelligence quotient. We used paternal obesity as negative control exposure as it involves the same source of confounding than maternal obesity.ResultsThe percentage of obese mothers and fathers was 8% and 12%, respectively. In unadjusted models, children of obese mothers had lower scores than children of normal weight mothers in all McCarthy subscales. After adjustment, only the verbal subscale remained statistically significantly reduced (β: -2.8; 95% confidence interval: -5.3, -0.2). No associations were observed among obese fathers. Maternal and paternal obesity were associated with an increase in ADHD-related symptoms. Parental obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy obesity was associated with a reduction in offspring verbal scores at pre-school age. This study was funded by grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1)

DOI: 10.1016/j.trsl.2016.06.012 URL: http://www.sciencedirect.com/science/article/pii/S1931524416301050 Filiació URV: SI Inclòs a la memòria: SI Angiopoietin-like protein 8 (ANGPTL8), a protein implicated in lipid and glucose homeostasis, is present only in mammals, suggesting that it is involved in processes unique to these vertebrates such as pregnancy and homeothermy. We explored the role of ANGPTL8 in maternal-fetal crosstalk and its relationship with newborn adiposity. In a longitudinal analysis of healthy pregnant women, ANGPTL8 levels decreased progressively during pregnancy although remained higher than levels in the postpartum period. In a cross-sectional observational study of women with or without gestational diabetes mellitus (GDM), and their offspring, ANGPTL8 levels were higher in venous cord blood than those in maternal blood and were significantly lower in GDM patients than those in healthy women. Infants small for gestational age and with low-fat mass had the highest ANGPTL8 cord blood levels. Studies in vitro revealed that ANGPTL8 was secreted by brown adipocytes and its expression was increased in experimental models of white-to-brown fat conversion. In addition, ANGPTL8 induced the expression of markers of brown adipocytes. The high levels of ANGPTL8 found in fetal life together with its relationship with newborn adiposity and brown adipose tissue point to ANGPTL8 as a potential new player in the modulation of the thermogenic machinery during the fetal-neonatal transition.

Multiple pregnancy increases the risk of a range of adverse perinatal outcomes, including breastfeeding failure. However, studies on predictive factors of breastfeeding duration in preterm twin infants have a conflicting result. The purpose of this observational study was to compare feeding practices, at hospital discharge, of twin and singleton very low birth weight infants. The study is part of a prospective survey of a national Spanish cohort of very low birth weight infants (SEN1500) that includes 62 neonatal units. The study population comprised all infants registered in the network from 2002 to 2013. They were grouped into singletons and multiples. The explanatory variables were first analyzed using univariate models, subsequently, significant variables were analyzed simultaneously in a multiple stepwise backward model. During the twelve-year period, 32,770 very low birth weight infants were included in the database, of which 26.957 were discharged alive and included in this analysis. Nine thousand seven hundred and fifty-eight neonates were multiples, and 17,199 were singletons. At discharge, 31% of singleton infants were being exclusively breastfed, 43% were bottle-fed, and 26% were fed a combination of both. In comparison, at discharge, only 24% of multiple infants were exclusively breastfed, 43% were bottle-fed, and 33% were fed a combination of both (p &lt, 0.001). On multivariable analysis, twin pregnancy had a statistically significant, but small effect, on cessation of breastfeeding before discharge (OR 1.10, 95% CI: 1.02, 1.19). Risks of early in-hospital breastfeeding cessation were also independently associated with multiple mother-infant stress factors, such as sepsis, intraventricular hemorrhage, retinopathy, necrotizing enterocolitis, intubation, and use of inotropes. Instead, antibiotic treatment at delivery, In vitro fertilization and prenatal steroids were associated with a decreased risk for shorter in-hospital breastfeeding duration. Multiple pregnancy, even in the absence of pathological conditions associated to very low birth weight twin infants, may be an impeding factor for in-hospital breastfeeding.

Endoplasmic reticulum (ER) homeostasis is crucial to appropriate cell functioning, and when disturbed, a safeguard system called unfolded protein response (UPR) is activated. Fructose consumption modifies ER homeostasis and has been related to metabolic syndrome. However, fructose sweetened beverages intake is allowed during gestation. Therefore, we investigate whether maternal fructose intake affects the ER status and induces UPR. Thus, administrating liquid fructose (10% w/v) to pregnant rats partially activated the ER-stress in maternal and fetal liver and placenta. In fact, a fructose-induced increase in the levels of pIRE1 (phosphorylated inositol requiring enzyme-1) and its downstream effector, X-box binding protein-1 spliced form (XBP1s), was observed. XBP1s is a key transcription factor, however, XBP1s nuclear translocation and the expression of its target genes were reduced in the liver of the carbohydrate-fed mothers, and specifically diminished in the fetal liver and placenta in the fructose-fed mothers. These XBP1s target genes belong to the ER-associated protein degradation (ERAD) system, used to buffer ER-stress and to restore ER-homeostasis. It is known that XBP1s needs to form a complex with diverse proteins to migrate into the nucleus. Since methylglyoxal (MGO) content, a precursor of advanced glycation endproducts (AGE), was augmented in the three tissues in the fructose-fed mothers and has been related to interfere with the functioning of many proteins, the role of MGO in XBP1s migration should not be discarded. In conclusion, maternal fructose intake produces ER-stress, but without XBP1s nuclear migration. Therefore, a complete activation of UPR that would resolve ER-stress is lacking. A state of fructose-induced oxidative stress is probably involved.

Introduction: The analysis of patients&rsquo, satisfaction with healthcare is recognised as being useful in the evaluation of health outcomes and perceived quality of care. Little is known, however, about how the psychological status of women who experience perinatal complications may affect their perceived satisfaction with care. Methods: We assessed healthcare satisfaction in 52 women who had undergone intrauterine surgery during a complicated monochorionic twin pregnancy and examined the influence that fetal loss and sociodemographic, clinical, and psychological factors had on the degree of satisfaction. Data were gathered in an individual interview and through the administration of the Medical Patient Satisfaction Questionnaire, Beck Depression Inventory, and State&ndash, Trait Anxiety Inventory. Relationships between variables were analysed using a chi-square test, Spearman&rsquo, s rho, Student&rsquo, s t test, and the Mann&ndash, Whitney U test, in accordance with the metric nature of the variables and the assumptions fulfilled. Results: Age and level of education were not associated with the degree of healthcare satisfaction. Negative but non-significant correlations were observed between the level of satisfaction and symptoms of anxiety and depression. Satisfaction with healthcare was high in the sample as a whole, although it was significantly higher among women who had not experienced fetal loss. There were no differences in satisfaction with services involving direct contact with medical staff, whereas satisfaction with indirect services was lower among women who had experienced perinatal loss. Conclusions: Due to the unique characteristics of this population, specialised care teams of both professional healthcare and indirect services are needed. Although administrative aspects of healthcare are regarded as being of secondary importance, this may not be the case with more vulnerable populations.

Background Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. Despite the frequently aggressive clinical nature, choriocarcinoma has been routinely curable with cytotoxic chemotherapy for over 50 years. To date little is known regarding the route to oncogenesis in this malignancy. Methods In a case of intraplacental choriocarcinoma, we have performed detailed genetic studies including microsatellite analysis, whole genome sequencing (WGS) and methylation analysis of the tumour and surrounding mature placenta. Results The results of the WGS sequencing indicated a very low level of mutation and the absence of any driver mutations or oncogene activity in the tumour. The methylation analysis identified a distinctly different profile in the tumour from that of the mature placenta. Comparison with a panel of reference methylation profiles from different stages of placental development indicated that the tumour segregated with the first trimester samples. Conclusions These findings suggest that gestational choriocarcinoma is likely to arise as a result of aberrations of methylation during development, rather than from DNA mutations. The results support the hypothesis that gestational choriocarcinoma arises from a normally transient early trophoblast cell. At this point in development this cell naturally has a phenotype of rapid division, tissue invasion and sensitivity to DNA damaging chemotherapy that is very similar to that of the mature choriocarcinoma cell. Electronic supplementary material The online version of this article (10.1186/s12885-019-5906-8) contains supplementary material, which is available to authorized users.

Background Obstetric complications have long been retrospectively associated with a wide range of short- and long-term health consequences, including neurodevelopmental alterations such as those observed in schizophrenia and other psychiatric disorders. However, prospective studies assessing fetal well-being during pregnancy tend to focus on perinatal complications as the final outcome of interest, while there is a scarcity of postnatal follow-up studies. In this study, the cerebroplacental ratio (CPR), a hemodynamic parameter reflecting fetal adaptation to hypoxic conditions, was analyzed in a sample of monozygotic monochorionic twins (60 subjects), part of them with prenatal complications, with regard to (i) epigenetic age acceleration, and (ii) DNA methylation at genes included in the polygenic risk score (PRS) for schizophrenia, and highly expressed in placental tissue. Results Decreased CPR measured during the third trimester was associated with epigenetic age deceleration (β = 0.21, t = 3.362, p = 0.002). Exploration of DNA methylation at placentally expressed genes of the PRS for schizophrenia revealed methylation at cg06793497 (EP300 gene) to be associated with CPR (β = 0.021, t = 4.385; p = 0.00008, FDR-adjusted p = 0.11). This association was reinforced by means of an intrapair analysis in monozygotic twins discordant for prenatal suffering (β = 0.027, t = 3.924, p = 0.001). Conclusions Prenatal adverse environment during the third trimester of pregnancy is associated with both (i) developmental immaturity in terms of epigenetic age, and (ii) decreased CpG-specific methylation in a gene involved in hypoxia response and schizophrenia genetic liability. Electronic supplementary material The online version of this article (10.1186/s13148-019-0674-5) contains supplementary material, which is available to authorized users.

Neonates are born with an immature immune system, which develops during the first stages of life. This early immaturity is more acute in preterm newborns. The aim of the present study was to set up a preterm rat model, in which representative biomarkers of innate and adaptive immunity maturation that could be promoted by certain dietary interventions are established. Throughout the study, the body weight was registered. To evaluate the functionality of the intestinal epithelial barrier, in vivo permeability to dextrans was measured and a histomorphometric study was performed. Furthermore, the blood cell count, phagocytic activity of blood leukocytes and plasmatic immunoglobulins (Ig) were determined. Preterm rats showed lower erythrocyte and platelet concentration but a higher count of leukocytes than the term rats. Although there were no changes in the granulocytes&rsquo, ability to phagocytize, preterm monocytes had lower phagocytic activity. Moreover, lower plasma IgG and IgM concentrations were detected in preterm rats compared to full-term rats, without affecting IgA. Finally, the intestinal study revealed lower permeability in preterm rats and reduced goblet cell size. Here, we characterized a premature rat model, with differential immune system biomarkers, as a useful tool for immunonutritional studies aimed at boosting the development of the immune system.

Resumen Objetivo Conocer a traves de las narraciones de las matronas de Atencion Primaria los factores que obstaculizan o contribuyen a la deteccion y el abordaje de la violencia de genero durante el embarazo, asi como sus propuestas de mejora para tal fin. Metodo Estudio cualitativo con un enfoque fenomenologico interpretativo. Se hicieron entrevistas semiestructuradas a las 12 matronas que trabajan en los centros de Atencion Primaria de L’Hospitalet de Llobregat (Barcelona). Resultados Las dificultades en la deteccion se relacionan con el sistema de visitas, el contexto de las mujeres y barreras del propio profesional como el miedo. Destacan como factores facilitadores el seguimiento en el control del embarazo y la relacion de confianza con la matrona. Las propuestas de mejora se relacionan con la formacion y el uso de procedimientos seguros y fiables. Conclusiones Seria deseable poner en marcha acciones de mejora, tales como ampliar la formacion y consensuar un circuito interno de trabajo que incluya instrumentos objetivos de ayuda de la deteccion, la coordinacion con otros servicios y la forma etica, y legalmente adecuada de registro en la historia clinica.

Background Limited health research capacities (HRC) undermine a country’s ability to identify and adequately respond to local health needs. Although numerous interventions to strengthen HRC have been conducted in Africa, there is a need to share the lessons learnt by funding organizations, institutes and researchers. The aim of this report is to identify best practices in HRC strengthening by describing a training programme conducted between 2016 and 2017 at the Saint Joseph’s Catholic Hospital (SJCH) in Monrovia (Liberia). Methods A call for trainees was launched at the SJCH, the Liberia Medicines and Health Products Regulatory Authority (LMHRA), the Ministry of Health and Social Welfare, the Mother Pattern College of Health Sciences (MPCHS) and community members. Selected trainees participated in four workshops on Good Clinical Laboratory Practice (GCLP), standard operating procedures (SOP) and scientific communication, as well as in a 5-months eLearning mentoring programme. After the training, a collectively-designed research project on malaria was conducted. Results Twenty-one of the 28 trainees (14 from the SJCH, 3 from LMHRA, one from MPCHS, and 10 community representatives) completed the programme satisfactorily. Pre- and post-training questionnaires completed by 9 of the trainees showed a 14% increase in the percentage of correct answers. Trainees participated in a mixed-methods cross-sectional study of Plasmodium falciparum infection among pregnant women at the SJCH. Selected trainees disseminated activities and research outcomes in three international meetings and three scientific publications. Conclusion This training-through-research programme successfully involved SJCH staff and community members in a practical research exercise on malaria during pregnancy. The challenge is to ensure that the SJCH remains active in research. Harmonization of effectiveness indicators for HRC initiatives would strengthen the case for investing in such efforts. Electronic supplementary material The online version of this article (10.1186/s12936-019-2767-1) contains supplementary material, which is available to authorized users.

Background Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Methods Eligible participants are women presenting at 20 to Discussion The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children’s neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. Trial registration NCT02996630, on 4th December 2016 (retrospectively registered).

Inorganic arsenic (i-As) is a non-threshold human carcinogen that has been associated with several adverse health outcomes. Exposure to i-As is of particular concern among pregnant women, infants and children, as they are specifically vulnerable to the adverse health effects of i-As, and in utero and early-life exposure, even low to moderate levels of i-As, may have a marked effect throughout the lifespan. Ion chromatography-mass spectrometry detection (IC-ICP-MS) was used to analyse urinary arsenic speciation, as an exposure biomarker, in samples of 4-year-old children with relatively low-level arsenic exposure living in different regions in Spain including Asturias, Gipuzkoa, Sabadell and Valencia. The profile of arsenic metabolites in urine was also determined in samples taken during pregnancy (1st trimester) and in the children from Valencia of 7 years old. The median of the main arsenic species found in the 4-year-old children was 9.71 mug/l (arsenobetaine-AsB), 3.97 mug/l (dimethylarsinic acid-DMA), 0.44 mug/l (monomethylarsonic acid-MMA) and 0.35 mug/l (i-As). Statistically significant differences were found in urinary AsB, MMA and i-As according to the study regions in the 4-year-old, and also in DMA among pregnant women and their children. Spearman's correlation coefficient among urinary arsenic metabolites was calculated, and, in general, a strong methylation capacity to methylate i-As to MMA was observed.

Maternal pertussis vaccination is associated with higher levels of pertussis antibodies at birth. We assessed the persistence of pertussis antibodies until primary vaccination in infants whose mothers received Tdap (tetanus, diphtheria, acellular pertussis) vaccine during pregnancy. Infants were born at the Hospital Clinic of Barcelona (Spain) in November 2014. Anti-PT IgG was determined by ELISA at delivery, between the first and second month of life, and estimated at 2months of age. The study included 37 infants whose mothers received Tdap between 21 and 38weeks of gestation. Infants presented a decline in GMC of anti-PT IgG between peripartum and follow-up levels, 52.7 (95% CI 34.7-80.2) versus 7.5 (95% CI 4.2-13.3) at 2months of age (p

Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax–infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1β, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition., European Union Seventh Framework Programme (FP7/2007-2013) 201588, Ministerio de Economia y Competitividad (National R&D Internationalization Programme, EUROSALUD 2008, Spain) EUS2009-03560, Centers for Disease Control and Prevention (CDC) Foundation, Malaria in Pregnancy Consortium (MiPc) - Bill & Melinda Gates Foundation 46099, MiPc, Spanish Government RYC-2008-02631, National Health and Medical Research Council of Australia GNT1043345

Few studies have investigated longitudinal associations between early life phthalate exposure and subsequent obesity and cardiovascular risks in children with inconsistent results. We aimed to evaluate the associations between phthalate exposure during gestation and childhood with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the Rhea pregnancy cohort in Crete, Greece. Seven phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were quantified in spot urine samples collected from mothers (1st trimester) and their children at 4 years of age. We calculated the molar sum of DEHP metabolites (MEHP, MEHHP, MEOHP). We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP), and lipids at 4 and 6 years and leptin, adiponectin, and C-reactive protein at 4 years. We used generalized estimating equations to examine associations at each age and tested for interaction by sex. Child exposure to phthalate metabolites was associated with lower BMI z-scores in boys and higher BMI z-scores in girls. Each 10-fold increase in ΣDEHP was associated with a change in waist circumference of -2.6 cm (95% CI: -4.72, -0.48) in boys vs. 2.14 cm (95% CI: -0.14, 4.43) in girls (p-sex interaction = 0.003) and a change in waist-to-height ratio of -0.01 (95% CI: -0.03, 0.01) in boys vs. 0.02 (95% CI: 0.01, 0.04) in girls (p-sex interaction = 0.006). Phthalate metabolite concentrations at age 4 were negatively associated with systolic and diastolic blood pressure. MEP was associated with lower systolic BP z-scores (adj. β = -0.22; 95% CI: -0.36, -0.08) at 4 years. MnBP and MBzP were associated with lower diastolic BP z-scores (adj. β = -0.13; 95%CI: -0.23, -0.04, and adj. β = -0.11; 95% CI: -0.21, -0.01, respectively). A 10-fold increase in MiBP was associated with 4.4% higher total cholesterol levels (95% CI: 0.2, 8.7). Prenatal phthalate exposure was not consistently associated with child adiposity and cardiometabolic measures. Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH- 2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7- HEALTH-2012 Proposal No 308333 HELIX, FP7 European Union project, No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15).

Progress indicators in maternal health in many low- and middle-income countries (LMICs) continue to fall below international standards despite Millennium Development Goal commitments and Sustainable Development Goal (SDG) aspirations [1]. While maternal mortality has fallen by 44% globally since 1990, many countries will struggle to meet the SDG target of fewer than 70 maternal deaths per 100,000 live births by 2030 [2]. Despite substantial efforts, globally over 300,000 women still die each year during pregnancy, childbirth, or the postpartum period, mostly from preventable causes. The burden of morbidity and mortality is inequitable, with vulnerable and marginalized populations at greatest risk. Although this burden disproportionately occurs in LMICs, it also affects increasing numbers of women in some high-income countries [3]. Improved counts of so-called indirect causes highlight the importance of nonobstetric morbidity during pregnancy, contributing around one-third of maternal deaths in LMICs [4]. Indirect causes include the effects of infections, noncommunicable diseases (NCDs), and mental health disorders. These highly prevalent conditions overlap and co-occur such that many women experience multimorbidity during and around pregnancy.

The enzyme FASN (fatty acid synthase) is potentially related with hypertension and metabolic dysfunction. FASN is highly expressed in the human placenta. We aimed to investigate the relationship circulating FASN has with blood pressure, maternal metabolism and newborn parameters in healthy pregnant women. Circulating FASN was assessed in 115 asymptomatic pregnant women in the second trimester of gestation along with C-peptide, fasting glucose and insulin, post-load glucose lipids, HMW-adiponectin and blood pressure (the latter was assessed in each trimester of gestation). At birth, newborns and placentas were weighed. FASN expression was also able to be assessed in 80 placentas. Higher circulating FASN was associated with lower systolic blood pressure (SBP), with a more favourable metabolic phenotype (lower fasting glucose and insulin, post load glucose, HbAc1, HOMA-IR and C-peptide), and with lower placental and birth weight (all p FASN expression related positively to circulating FASN (p

BACKGROUND: Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, TNF, TNF-beta was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-gamma, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR. RESULTS: Higher concentrations of IL-6 and IL-1beta were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1beta and TNF strongly correlated among themselves (rho > 0.5, p < 0.001). Higher production of IL-1beta was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044). CONCLUSIONS: Complex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection.

BACKGROUND: Difficulties to disentangle the protective versus exposure role of anti-malarial antibodies hamper the identification of clinically-relevant immune targets. Here, factors affecting maternal IgG and IgMs against Plasmodium falciparum antigens, as well as their relationship with parasite infection and clinical outcomes, were assessed in mothers and their children. Antibody responses among 207 Mozambican pregnant women at delivery against MSP119, EBA175, AMA1, DBLalpha and parasite lysate (3D7, R29 and E8B parasite lines), as well as the surface of infected erythrocytes, were assessed by enzyme-linked immunosorbent assay and flow cytometry. The relationship between antibody levels, maternal infection and clinical outcomes was assessed by multivariate regression analysis. RESULTS: Placental infection was associated with an increase in maternal levels of IgGs and IgMs against a broad range of parasite antigens. The multivariate analysis including IgGs and IgMs showed that the newborn weight increased with increasing IgG levels against a parasite lysate, whereas the opposite association was found with IgMs. IgGs are markers of protection against poor pregnancy outcomes and IgMs of parasite exposure. CONCLUSIONS: Adjusting the analysis for the simultaneous effect of IgMs and IgGs can contribute to account for heterogeneous exposure to P. falciparum when assessing immune responses effective against malaria in pregnancy.

The current prescription of clozapine in psychotic women of reproductive age makes it crucial to understand its pharmacokinetics during pregnancy and lactation as well as its risk profile for neonatal outcome. The aim of this case series was to provide new evidence on the pharmacokinetic features of clozapine that determine its passage through the placenta and amniotic fluid, as well as the neonatal clozapine elimination half-life (t1/2). This case series demonstrates for the first time that clozapine might show partial placental passage similar to other atypical antipsychotics. Clozapine levels decreased during the first few days in nursing infants. The half-life of clozapine in neonates was slightly higher than previously estimated. Clozapine use in pregnancy may be associated with diabetes mellitus, especially if there is a family history of this disease. Although no acute toxicological effects were observed in the intrauterine exposed newborn, close follow-up of pregnancy is recommended. However, these results must be taken with caution being a case series with small sample size, The study was supported by the Generalitat de Catalunya/Support a les activitats del Grups de Recerca: SGR2017/1798.

Objective: To evaluate left myocardial performance index (MPI) and time intervals in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser surgery. Methods: Fifty-one fetal pairs with TTTS and 47 uncomplicated monochorionic twin pairs were included. Left ventricular isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured using conventional Doppler. Results: Recipients showed prolonged ICT (46 ± 12 vs. 31 ± 8 vs. 30 ± 5 ms; p < 0.001) and IRT (51 ± 9 vs. 43 ± 8 vs. 43 ± 5 ms; p < 0.001) and higher MPI (0.57 ± 0.12 vs. 0.47 ± 0.09 vs. 0.44 ± 0.05; p < 0.001) than donors and controls. Donors showed shorter ET than recipients and controls (157 ± 12 vs. 169 ± 10 vs. 168 ± 10 ms; p < 0.001) and higher MPI than controls (0.47 ± 0.09 vs. 0.44 ± 0.05; p = 0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals partially improved after surgery. Conclusion: Donor and recipient twins had higher MPI due to different changes in the time intervals, possibly reflecting the state of hypovolemia in the donor and hypervolemia and pressure overload in the recipient.

Malaria in pregnancy threatens birth outcomes and the health of women and their newborns. This is also the case in low transmission areas, such as Colombia, where Plasmodium vivax is the dominant parasite species. Within the Colombian health system, which underwent major reforms in the 90s, malaria treatment is provided free of charge to patients. However, patients still incur costs, such as transportation and value of time lost due to the disease. We estimated such costs among 40 pregnant women with clinical malaria (30% Plasmodium falciparum, 70% Plasmodium vivax) in the municipality of Tierralta, Northern Colombia. In a cross-sectional study, women were interviewed after an outpatient or inpatient laboratory confirmed malaria episode. Women were asked to report all types of cost incurred before (including prevention), during and immediately after the contact with the health facility. Median total cost was over 16US$ for an outpatient visit, rising to nearly 30US$ if other treatments were sought before reaching the health facility. Median total inpatient cost was 26US$ or 54US$ depending on whether costs incurred prior to admission were excluded or included. For both outpatients and inpatients, direct costs were largely due to transportation and indirect costs constituted the largest share of total costs. Estimated costs are likely to represent only one of the constraints that women face when seeking treatment in an area characterized, at the time of the study, by armed conflict, displacement, and high vulnerability of indigenous women, the group at highest risk of malaria. Importantly, the Colombian peace process, which culminated with the cease-fire in August 2016, may have a positive impact on achieving universal access to healthcare in conflict areas. The current study can inform malaria elimination initiatives in Colombia., Author summary Malaria in pregnancy is a harsh and undesirable illness and is the cause of adverse effects on birth outcomes and on the health of women and newborns. Despite the low transmission, the predominance of Plasmodium vivax over Plasmodium falciparum and free treatment, estimated costs incurred by pregnant women seeking malaria care in an endemic area of Northern Colombia are considerable. Importantly, these costs are likely to represent only one of the constraints that women face when seeking treatment in an area characterized, at the time of the study, by armed conflict, displacement, and high vulnerability of indigenous women, the group at highest risk of malaria in the area. Important advances may result from the current peace process, potentially able to support the efforts made since the 90s to reform the health system towards achieving universal health coverage. Within this context, the current study can inform malaria elimination initiatives in Colombia.

Cadmium (Cd) is a non-physiological heavy metal that can be harmful at low concentrations. Increasing anthropogenic activities are incrementing the risk of accumulation of this heavy metal in different organs and tissues of the body. In the case of pregnant women, the threat is more serious due to the implications affecting not only their own health but also fetal development as well. Metallothioneins (MTs), small cysteine-rich proteins, are involved in zinc (Zn) and copper homeostasis in mammals but can, however, also bind with Cd if present. The accumulation of Cd in maternal tissues (e.g. placenta, maternal blood, and mammary glands) induces the synthesis of MTs, preferably MT2, in an attempt to sequester the metal to avoid toxicity. The formed Cd–MT complexes will avoid the Cd transport from the placenta to the fetus and end up accumulating in the maternal kidneys. At the same time, high concentrations of MTs will increase the formation of Zn–MT complexes, therefore decreasing the amount of Zn ions available to be transported to the fetus by means of Zn transporters such as ZnT2, ZIP14 and DMT1. Although MTs cannot transport Cd from the mother to the fetus, the divalent DMT1 transporter is suggested to carry the metal to the fetus. As a consequence, the low levels of Zn(II) in the fetus, together with the presence of Cd(II) coming from the mother either via the placenta and cord blood or via breast milk induce changes in the fetal development including fetal growth retardation, and low weight or height of the newborn. Likewise, the concentrations of Cd(II) in the newborn can cause alterations such as cognitive disabilities. In summary, the presence of Cd(II) in the maternal tissues will induce MT synthesis in an attempt to detoxify these tissues and reduce the possible toxicity of Cd in fetal and newborn tissues

Background At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. Conclusion The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa.

Background Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia. Conclusions GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.

Altres ajuts: RecerCaixa (OG085818) Fundación Mútua Madrileña (AP150572014) Alcohol and drugs of abuse consumption in young adults, including women of childbearing age, has experienced significant increase over the past two decades. The use of questionnaires as the only measure to investigate prenatal alcohol and drugs of abuse exposure underestimates the real prevalence of exposure and could mislead to wrong conclusions. Therefore, the aim of this article was to compare reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers of exposure by a comprehensive review of the available literature. We searched MEDLINE and EMBASE databases for articles catalogued between 1992 and 2015. We identified relevant published studies that assessed the comparison between prenatal exposure to alcohol and drugs of abuse assessed by self-reported questionnaire of consumption versus biomarkers of exposure. Thirteen studies were included regarding alcohol consumption, and seven of them about drugs of abuse. Women who admitted consumption during pregnancy by questionnaire varied from 0 to 37% for alcohol, from 0 to 4.3% for cocaine, and 2.9% for tetrahydrocannabinol (THC). Positive biomarkers results ranged from 16 to 44% for alcohol, 15.4% for cocaine, and from 4 to 12.4% for THC. Biomarkers should always complement questionnaires, as it has been shown that self-report may underestimate prenatal exposure to substances of abuse.

BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG). METHODS: Placental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14-26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection. RESULTS: Of 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76-7.51; p