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Effects of Zika infection on growth.
Prata-Barbosa, A, Martins, MM, Guastavino, AB, Cunha, AJLAD
Jornal de pediatria. 2019;:30-41
Abstract
OBJECTIVES To present the currently available evidence of the effects of congenital Zika virus infection on infant growth, to discuss possible intervening factors, and to describe preliminary data on this growth in a cohort of exposed children. SOURCE OF DATA Non-systematic review in PubMed, BVS, CAPES, Scopus, Web of Science, Cochrane and Google Scholar databases in the last 5 years, using the terms infection/disease by Zika virus and growth/nutrition/nutritional status/infant nutrition and nutritional needs. Additionally, the anthropometric data of the first 2.5 years of a cohort of children exposed to the Zika virus during pregnancy were reviewed. SYNTHESIS OF DATA Both intrauterine growth restriction and low birth weight were reported in series of cases of children with congenital Zika syndrome. The postnatal growth deficit of these children appears to be directly proportional to the degree of neurological impairment. The etiology is multifactorial, and nutritional and non-nutritional factors are probably involved. The data from the present cohort show that the head circumference evolution depends on this measurement at birth and that weight-height growth has a trend toward lower weight and length in children with congenital microcephaly and normocephalic at birth who develop some neurological abnormality. CONCLUSIONS The few existing data suggest that, in children with congenital Zika, the greater the degree of neurological impairment, the greater the impact on growth, whether or not associated with microcephaly at birth.
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Maternal infection with Zika virus and prevalence of congenital disorders in infants: systematic review and meta-analysis.
Nithiyanantham, SF, Badawi, A
Canadian journal of public health = Revue canadienne de sante publique. 2019;(5):638-648
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OBJECTIVE Zika virus (ZIKV) infection is a vector-borne disease that can be transmitted sexually and vertically. The vertical transmission of the virus may lead to congenital Zika syndrome in infants. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of congenital Zika-related disorders in infants of mothers infected with ZIKV during pregnancy. METHODS We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic and Web of Science databases to identify human studies reporting prevalence of congenital disorders in infants of ZIKV-infected mothers. RESULTS We identified 25 reports selected for inclusion in the current study (n = 4683 subjects). The majority of the studies were from South American high-risk countries. Only one third of the identified studies were conducted in the United States. Clinical maternal symptoms included maculopapular rash (76.9%), arthralgia (46.4%), fever (45.5%) and headache (31.8%) with myalgia and conjunctivitis only presented in 25% of the cases. The most prevalent congenital disorder in the newborns was brain calcifications (42.6; 95% CI, 30.8-54.4), followed by ventriculomegaly (21.8; 95% CI, 15.2-28.4), joint abnormalities (13.2; 95% CI, 9.4-18.2), ocular abnormalities (4.2; 95% CI, 1.0-7.5) and microcephaly (3.9; 95% CI, 2.4-5.4). CONCLUSION The current study highlights the high prevalence of a range of congenital disorders in newborns of mothers infected with ZIKV. It warrants developing studies to further clarify the mechanisms by which each of these disorders occurs in response to the viral infection during pregnancy and its vertical transmission to the infants.
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Brief Report: Surveillance of Congenital Anomalies After Exposure to Raltegravir or Elvitegravir During Pregnancy in the United Kingdom and Ireland, 2008-2018.
Rasi, V, Cortina-Borja, M, Peters, H, Sconza, R, Thorne, C
Journal of acquired immune deficiency syndromes (1999). 2019;(3):264-268
Abstract
BACKGROUND The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland. METHODS The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure. RESULTS A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion. CONCLUSIONS The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.
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Maternal anemia type during pregnancy is associated with anemia risk among offspring during infancy.
Abioye, AI, McDonald, EA, Park, S, Ripp, K, Bennett, B, Wu, HW, Pond-Tor, S, Sagliba, MJ, Amoylen, AJ, Baltazar, PI, et al
Pediatric research. 2019;(3):396-402
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BACKGROUND We evaluated the association between etiology of maternal anemia and iron status throughout infancy. METHODS Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated. RESULTS Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status. CONCLUSIONS Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.
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HIV infection and increased food insecurity are associated with adverse body composition changes among pregnant and lactating Kenyan women.
Widen, EM, Tsai, I, Collins, SM, Wekesa, P, China, J, Krumdieck, N, Miller, JD, Weiser, SD, Onono, M, Young, SL
European journal of clinical nutrition. 2019;(3):474-482
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BACKGROUND/OBJECTIVES Body composition changes markedly during reproduction. In sub-Saharan Africa, impacts of HIV infection on body composition across pregnancy and lactation in the context of Option B+ antiretroviral therapy are unknown. Therefore, we sought to evaluate the role of HIV infection on body composition during pregnancy and lactation among Kenyan women. SUBJECTS/METHODS A cohort of pregnant women (n = 333; 50.5% HIV+, receiving ART) were enrolled at seven clinics in western Kenya. Two prenatal (mean ± SD: 23.6 ± 4.4 and 33.4 ± 2.0 weeks gestation) and three postpartum (6, 14, and 36 weeks) measurements included: individual-level food insecurity, height, weight, fat mass (FM), and fat-free mass (FFM) by bioimpedance analysis (BIA), mid-upper arm circumference (MUAC), and triceps skinfold (TSF), allowing for AMA (arm muscle area) and AFA (arm fat area) derivation. Multivariable longitudinal regression models were used to relate HIV to body composition changes. RESULTS In longitudinal models, HIV-infected women had lower weight (ß = -3.0 kg, p = 0.003), fat mass (ß = -1.5 kg, p = 0.02), fat-free mass (ß = -1.5 kg, p = 0.01), TSF (ß = -2.6 mm, p < 0.001), AFA (ß = -3.9 cm3, p < 0.001), and MUAC (ß = -1.0 cm, p = 0.001), but not AMA (p = 0.34), across all observations. Food insecurity was inversely associated with AMA and MUAC postpartum (AMA ß-range = -0.47 to -0.92 cm3; MUAC ß-range = -0.09 to -0.15 cm, all p < 0.05). CONCLUSIONS HIV infection was associated with lower weight, fat mass, fat-free mass, TSF, AFA, and MUAC values during pregnancy and lactation, while food insecurity was intermittently associated with body composition. This suggests that pregnant and lactating women living with HIV and food insecurity could benefit from nutritional support.
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Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.
Mannucci, C, Dante, G, Miroddi, M, Facchinetti, F, D'Anna, R, Santamaria, A, Lenti, MC, Vannacci, A, Calapai, F, Perone, M, et al
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(1):125-128
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PURPOSE Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. MATERIALS AND METHODS On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. RESULTS Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. CONCLUSIONS Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.
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International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.
Lebov, JF, Arias, JF, Balmaseda, A, Britt, W, Cordero, JF, Galvão, LA, Garces, AL, Hambidge, KM, Harris, E, Ko, A, et al
BMC pregnancy and childbirth. 2019;(1):282
Abstract
BACKGROUND Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. METHODS At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. DISCUSSION With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. TRIAL REGISTRATION NCT02856984 . Registered August 5, 2016. Retrospectively registered.
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New-onset ulcerative colitis in pregnancy associated to toxic megacolon and sudden fetal decompensation: Case report and literature review.
Brunelli, R, Perrone, S, Perrone, G, Galoppi, P, De Stefano, MG, Maragno, AM, Cesarini, M, De Carolis, A, Masselli, G, Vernia, P
The journal of obstetrics and gynaecology research. 2019;(7):1215-1221
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease rarely arising during gestation. Because the available information is based on case reports or small retrospective studies, diagnosis may be difficult and treatment is still controversial. A case of toxic megacolon developing in late pregnancy associated to a sudden fetal decompensation is described. Diagnostic and clinical topics of acute UC onset in pregnancy are debated.A primipara, 34 years old, 33/0 weeks of gestation, was admitted with a diagnosis of preterm labor, associated to acute bloody diarrhea (up to 10 daily motions) and cramping abdominal pain. A diagnosis of new-onset early-stage UC was made by sigmoidoscopy. An intensive care regimen including hydrocortisone, antibiotics and parenteral nutrition was immediately started. Magnetic resonance imaging of maternal abdomen, fostered by the worsening patient conditions, evidenced dilatation of the entire colon and a severely hampered of fetal muscular tone.Toxic megacolon complicated by superimposed Clostridium difficile infection was associated to a sudden fetal decompensation diagnosed by chance during maternal abdominal magnetic resonance imaging. An emergency cesarean section was mandatory. According to a senior surgeon's decision, total colectomy was not immediately performed following cesarean section with reference to the absence of colonic perforation. We obtained a good short-term maternal outcome and an uncomplicated neonatal course. Counseling of those patients must be focused on timely and multidisciplinary intervention in order to improve the course of maternal disease and to prevent fetal distress.
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Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV.
Hodel, EM, Marzolini, C, Waitt, C, Rakhmanina, N
Current pharmaceutical design. 2019;(5):556-576
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BACKGROUND Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants. METHODS We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively. RESULTS We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs. CONCLUSIONS Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter's role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.
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HIV Exposure and Formula Feeding Predict Under-2 Mortality in HIV-Uninfected Children, Botswana.
Ajibola, G, Leidner, J, Mayondi, GK, van Widenfelt, E, Madidimalo, T, Petlo, C, Moyo, S, Mmalane, M, Williams, PL, Cassidy, AR, et al
The Journal of pediatrics. 2018;:68-75.e2
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OBJECTIVES To prospectively assess rates and detailed predictors of morbidity and mortality among HIV-exposed uninfected children and HIV-unexposed children in Botswana in a more recent era. STUDY DESIGN We enrolled HIV-infected and HIV-uninfected mothers and their children in the prospective observational Tshipidi study at 2 sites (1 city and 1 village) in Botswana from May 2010-July 2012. Live-born children and their mothers were followed for 24 months postpartum. Detailed sociodemographic data, health, and psychosocial characteristics were collected at baseline and prospectively, and health outcomes ascertained. Mothers chose infant feeding method with counselling. RESULTS A total of 893 live-born HIV-uninfected children (436 HIV-exposed uninfected, 457 HIV-unexposed) were followed. HIV-infected mothers had a median CD4 count of 410 cells/mm3, 32% took 3-drug antiretroviral treatment during pregnancy, 67% took only zidovudine, and 1% took <2 weeks of any antiretrovirals antepartum. Twenty four-month vital status was available for 888 (99.4%) children. HIV-exposed uninfected children had a significantly higher risk of death compared with children of HIV-uninfected mothers (5.0% vs 1.8%) (adjusted hazard ratio 3.27, 95% CI 1.44-7.40). High collinearity between maternal HIV status and child feeding method precluded analysis of these factors as independent predictors of mortality. Preterm birth, low birth weight, and congenital anomaly were also associated with mortality (in separate analyses), but maternal socioeconomic factors, depression, substance use, and social support were not significant predictors. CONCLUSIONS The strongest predictors of 24-month mortality among children in Botswana were HIV exposure and formula feeding, although the relative contribution of these factors to child health could not be separated.