Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study

Background The prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure. Methodology/Principal findings We performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1–24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3–26.9), with a PAF of 59.5%. Conclusions A significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

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Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

Viruses ◽

10.3390/v13081427 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1427

Author(s):

Paula Sobral da Silva ◽

Sophie Eickmann ◽

Ricardo Ximenes ◽

Celina Martelli ◽

Elizabeth Brickley ◽

...

Keyword(s):

Neurological Examination ◽

Zika Virus ◽

Control Group ◽

P Value ◽

Zikv Infection ◽

Clinical Neurological Examination ◽

Cognitive Delay ◽

Increased Risk ◽

Neurodevelopmental Impairment ◽

The Impact

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

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In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study

BMC Medicine ◽

10.1186/s12916-020-01888-0 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Rebecca Grant ◽

Olivier Fléchelles ◽

Benoît Tressières ◽

Mama Dialo ◽

Narcisse Elenga ◽

...

Keyword(s):

Cohort Study ◽

Zika Virus ◽

Population Based ◽

In Utero ◽

Fine Motor ◽

Neurodevelopmental Outcomes ◽

Zikv Infection ◽

Five Dimensions ◽

Ultrasound Findings ◽

The Impact

Abstract Background In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. Methods We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. Results Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. Conclusion In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. Trial registration ClinicalTrials.gov, NCT02810210. Registered 20 June 2016.

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Short- and long-term outcomes of preterm spontaneous twin anemia-polycythemia sequence

Journal of Perinatal Medicine ◽

10.1515/jpm-2019-0437 ◽

2020 ◽

Vol 48 (4) ◽

pp. 329-334

Author(s):

Soo Jin Han ◽

Seung Mi Lee ◽

Sohee Oh ◽

Subeen Hong ◽

Jeong Won Oh ◽

...

Keyword(s):

Cord Blood ◽

Neonatal Morbidity ◽

Adverse Outcomes ◽

Control Group ◽

Long Term Outcomes ◽

Neurodevelopmental Outcomes ◽

Monochorionic Twin ◽

Increased Risk ◽

Study Population

AbstractBackgroundIn monochorionic twin pregnancy, placental anastomosis and inter-twin blood transfusion can result in specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). It is well established that adverse outcomes are increased in TTTS, but reports on the neonatal and long-term outcomes of TAPS are lacking. The objective of this study was to evaluate the neonatal and neurodevelopmental outcomes in spontaneous TAPS.MethodsThe study population consisted of monochorionic twin pregnancies with preterm birth (24–37 weeks of gestation) between November 2003 and December 2016 and in which cord blood was taken at the time of delivery. According to the result of hemoglobin in cord blood, the study population was divided into two groups: a spontaneous TAPS group and a control group. Neonatal and neurodevelopmental outcomes were compared between the two groups.ResultsDuring the study period, 11 cases were diagnosed as spontaneous TAPS (6.4%). The TAPS group had lower gestational age at delivery and had a higher risk for cesarean delivery. However, neonates with TAPS were not at an increased risk for neonatal mortality and significant neonatal morbidity. In addition, the frequency of severe cerebral lesion during the neonatal period and the risk of cerebral palsy at 2 years of age were not different between the two groups.ConclusionThe spontaneous TAPS diagnosed by postnatal diagnostic criteria was not associated with the increased risk of adverse neonatal and neurodevelopmental outcomes. Further studies are needed to evaluate the morbidity of antenatally diagnosed TAPS.

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Inflammatory markers and risk of cardiovascular mortality in relation to diabetes status in the HUNT study

Scientific Reports ◽

10.1038/s41598-021-94995-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Løfblad ◽

Gunhild Garmo Hov ◽

Arne Åsberg ◽

Vibeke Videm

Keyword(s):

Cardiovascular Mortality ◽

Inflammatory Markers ◽

Cox Regression ◽

Population Based ◽

Control Group ◽

Bottom Quartile ◽

Diabetes Status ◽

Increased Risk ◽

General Populations ◽

Log Linear

AbstractInflammatory markers have been associated with increased risk of cardiovascular mortality in general populations. We assessed whether these associations differ by diabetes status. From a population-based cohort study (n = 62,237) we included all participants with diabetes (n = 1753) and a control group without diabetes (n = 1818). Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for possible associations with cardiovascular mortality of 4 different inflammatory markers; C-reactive protein (CRP), calprotectin, neopterin and lactoferrin. During a median follow-up of 13.9 years, 728 (20.4%) died from cardiovascular disease (CVD). After adjustment for age, sex and diabetes, the associations of all inflammatory markers with risk of cardiovascular mortality were log-linear (all P ≤ 0.017 for trend) and did not differ according to diabetes status (all P ≥ 0.53 for interaction). After further adjustments for established risk factors, only CRP remained independently associated with cardiovascular mortality. HRs were 1.22 (1.12–1.32) per standard deviation higher loge CRP concentration and 1.91 (1.50–2.43) when comparing individuals in the top versus bottom quartile. The associations of CRP, calprotectin, lactoferrin and neopterin with cardiovascular mortality did not differ by diabetes, suggesting that any potential prognostic value of these markers is independent of diabetes status.

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Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00767.x ◽

2007 ◽

Vol 17 (1) ◽

pp. 229-232 ◽

Cited By ~ 18

Author(s):

M. G. Junqueira ◽

I. D.C.G. Da Silva ◽

N. C. Nogueira-De-Souza ◽

C. V. Carvalho ◽

D. B. Leite ◽

...

Keyword(s):

Endometrial Cancer ◽

Progesterone Receptor ◽

Receptor Gene ◽

Population Based ◽

Cancer Development ◽

Control Group ◽

Cancer Group ◽

Increased Risk ◽

Progesterone Receptor Gene ◽

Risk Modifier

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The χ2 test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

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In utero exposure to ritodrine during pregnancy and risk of autism in their offspring until 8 years of age

Scientific Reports ◽

10.1038/s41598-020-80904-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jungsoo Chae ◽

Geum Joon Cho ◽

Min-Jeong Oh ◽

KeonVin Park ◽

Sung Won Han ◽

...

Keyword(s):

National Health ◽

Screening Program ◽

Hazard Analysis ◽

Population Based ◽

In Utero ◽

National Database ◽

Rank Test ◽

In Utero Exposure ◽

Exposure Group ◽

Increased Risk

AbstractBeta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their offspring. However, the particular link between autism and ritodrine, a common type of B2AR agonist used solely as tocolytics, has never been substantiated with any nationwide database. Thus, we aimed to examine the association between in utero exposure of ritodrine and the risk of autism in their offspring using a national database. This population-based cohort study was conducted by merging the Korea National Health Insurance claims database and National Health Screening Program for Infants and Children database. These databases included all women who had delivered singleton between January 2007 and December 2008 in Korea. Out of the total 770,016 mothers, 30,959 (4.02%) were exposed to ritodrine during pregnancy, and 5583 (0.73%) of their children were identified as having autism, defined until 8 years of age. According to our analysis, the overall cumulative incidence of autism up to 8 years was 1.37% in ritodrine exposure group and 0.70% in ritodrine non-exposure group (p < 0.05, log-rank test). By Cox proportional hazard analysis, use of ritodrine in preterm birth was associated with significantly higher hazard of autism [adjusted hazard ratio: 1.23, 95% CI 1.04–1.47], after adjusting for confounding variables including maternal age, parity, cesarean section, preterm labor, steroid use, birth weight, gender, and preeclampsia. Thus, in utero exposure to ritodrine was associated with an increased risk of autism in their offspring.

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Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study

The British Journal of Psychiatry ◽

10.1192/bjp.bp.111.092098 ◽

2012 ◽

Vol 200 (5) ◽

pp. 374-380 ◽

Cited By ~ 112

Author(s):

Shaw-Ji Chen ◽

Yu-Lin Chao ◽

Chuan-Yu Chen ◽

Chia-Ming Chang ◽

Erin Chia-Hsuan Wu ◽

...

Keyword(s):

Autoimmune Diseases ◽

Multiple Testing ◽

Pernicious Anaemia ◽

Population Based ◽

Control Group ◽

Research Database ◽

Population Based Study ◽

Hypersensitivity Vasculitis ◽

Increased Risk ◽

Specific Variation

BackgroundThe association between autoimmune diseases and schizophrenia has rarely been systematically investigated.AimsTo investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.MethodTaiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing.ResultsWhen compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04–1.67), psoriasis (OR = 1.48, 95% CI 1.07–2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04–2.80), celiac disease (OR = 2.43, 95% CI 1.12–5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64–15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35–0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis.ConclusionsSchizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.

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Pregnancy Outcome Following Gestational Exposure to Fluoroquinolones: a Multicenter Prospective Controlled Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.6.1336 ◽

1998 ◽

Vol 42 (6) ◽

pp. 1336-1339 ◽

Cited By ~ 157

Author(s):

Ronen Loebstein ◽

Antonio Addis ◽

Elaine Ho ◽

Roseann Andreou ◽

Suzanne Sage ◽

...

Keyword(s):

Relative Risk ◽

Confidence Interval ◽

Pregnancy Outcome ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

In Utero ◽

Controlled Study ◽

Control Group ◽

Increased Risk ◽

Clinically Significant

ABSTRACT Concerns regarding the teratogenicity of fluoroquinolones have resulted in their restricted use during gestation. This is despite an increasing need for their use due to emerging bacterial resistance. The objectives of the present investigation were to evaluate pregnancy and fetal outcomes following maternal exposure to fluoroquinolones and to examine whether in utero exposure to quinolones is associated with clinically significant musculoskeletal dysfunctions. We prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was compared with that for 200 controls matched for age and for smoking and alcohol consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic antimicrobial agents matched by indication, duration of therapy (±3 days), and trimester of exposure. Rates of major congenital malformations did not differ between the group exposed to quinolones in the first trimester (2.2%) and the control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to 3.49). Women treated with quinolones had a tendency for an increased rate of therapeutic abortions compared with the rate among women exposed to nonteratogens (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions, fetal distress, and prematurity and the birth weight did not differ between the groups. Gross motor developmental milestone achievements did not differ between the children of the mothers in the two groups. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary to the misperception of a major risk related to quinolone use during pregnancy.

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Anxiety and depression in parents 4–9 years after the loss of a child owing to a malignancy: a population-based follow-up

Psychological Medicine ◽

10.1017/s0033291704002740 ◽

2004 ◽

Vol 34 (8) ◽

pp. 1431-1441 ◽

Cited By ~ 133

Author(s):

ULRIKA KREICBERGS ◽

UNNUR VALDIMARSDÓTTIR ◽

ERIK ONELÖV ◽

JAN-INGE HENTER ◽

GUNNAR STEINECK

Keyword(s):

Psychological Distress ◽

Relative Risk ◽

Confidence Interval ◽

Stressful Life Event ◽

Population Based ◽

Anxiety And Depression ◽

Control Group ◽

Bereaved Parents ◽

Increased Risk ◽

Loss Of A Child

Background. Some consider the loss of a child as the most stressful life event. When the death is caused by a malignancy, the parents are commonly exposed not only to their own loss, but also to the protracted physical and emotional suffering of the child. We investigated parental risk of anxiety and depression 4–9 years after the loss of a child owing to a malignancy.Method. In 2001, we attempted to contact all parents in Sweden who had lost a child due to a malignancy during 1992–1997. We used an anonymous postal questionnaire and utilized a control group of non-bereaved parents with a living child.Results. Participation among bereaved parents was 449/561 (80%); among non-bereaved 457/659 (69%). We found an increased risk of anxiety (relative risk 1·5, 95% confidence interval 1·1–1·9) and depression (relative risk 1·4, 95% confidence interval 1·1–1·7) among bereaved parents compared with non-bereaved. The risk of anxiety and depression was higher in the period 4–6 years after bereavement than in the 7–9 years period, during which the average excess risks approached zero. Psychological distress was overall higher among bereaved mothers and loss of a child aged 9 years or older implied an increased risk, particularly for fathers.Conclusions. Psychological morbidity in bereaved parents decreases to levels similar to those among non-bereaved parents 7–9 years after the loss. Bereaved mothers and parents who lose a child 9 years or older have on average an excess risk for long-term psychological distress.

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Increased risk of cancer in patients with retinal vein occlusion: a 12-year nationwide cohort study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316947 ◽

2020 ◽

pp. bjophthalmol-2020-316947

Author(s):

Min Seok Kim ◽

Joon Hee Cho ◽

Seong Jun Byun ◽

Chang-Mo Oh ◽

Kyu Hyung Park ◽

...

Keyword(s):

Retinal Vein Occlusion ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Control Group ◽

Time Varying ◽

Vein Occlusion ◽

Increased Risk ◽

Risk Of Cancer ◽

Subsequent Cancer

AimsTo investigate the association between incident retinal vein occlusion (RVO) and the subsequent development of cancer.MethodsIn this nationwide population-based retrospective study using 2002–2013 National Health Insurance Service database which covers the entire South Korean population, 186 701 incident RVO patients and their 1:1 propensity-score matched controls were included. We defined the fixed cohort from January 1st, 2004 to December 31st, 2013; the cohort included patients who suffered incident RVO after entering the cohort and their matched controls, and excluded patients having any cancer history before entering the cohort. The association of RVO and cancer was assessed by time-varying covariate Cox regression models; Model 1 included RVO as a time-varying covariate, Model 2 included Model 1 plus demographic information and Model 3 included Model 2 and comorbidities.ResultsRVO was associated with an increased risk of subsequent cancer (HR=1.29; 95% CI, 1.26–1.31 in Model 1), which was consistent in Models 2 and 3. The incidence rate of overall cancer during the study period was 25.55 (95% CI, 25.19–25.91) per 1000 person-years in the RVO group and 18.62 (95% CI, 18.46–18.79) per 1000 person-years in the control group. In the subgroup analysis, haematological malignancies showed the highest association with RVO (HR=1.65; 95% CI, 1.49–1.83).ConclusionPatients with RVO have an increased risk of subsequent cancer development even after adjusting for demographic factors and comorbidities. Further study is warranted to elucidate these associations to provide proper recommendations for RVO patients regarding the cancer screening.

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