Offspring Of Pregnant Women Research Articles

Risk-prediction nomogram for congenital heart disease in offspring of Chinese pregnant women

BackgroundThe identification and assessment of environmental risks are crucial for the primary prevention of congenital heart disease (CHD). We were aimed to establish a nomogram model for CHD in the offspring of pregnant women and validate it using a large CHD database in Northwest China.MethodsA survey was conducted among 29,204 women with infants born between 2010 and 2013 in Shaanxi province, Northwest China. Participants were randomly assigned to the training set and to the validation set at a ratio of 7:3. The importance of predictive variables was assessed using random forest. A multivariate logistic regression model was used to construct the nomogram for the prediction of CHD.ResultsMultivariate analyses revealed that the gravidity, preterm birth history, family history of birth defects, infection, taking medicine, tobacco exposure, pesticide exposure and singleton/twin pregnancy were significant predictive risk factors for CHD in the offspring of pregnant women. The area under the receiver operating characteristic curve for the prediction model was 0.716 (95% CI: 0.671, 0.760) in the training set and 0.714 (95% CI: 0.630, 0.798) in the validation set, indicating moderate discrimination. The prediction model exhibited good calibration (Hosmer-Lemeshow χ2 = 1.529, P = 0.910).ConclusionsWe developed and validated a predictive nomogram for CHD in offspring of Chinese pregnant women, facilitating the early prenatal assessment of the risk of CHD and aiding in health education.

Maternal vitamin D intakes during pregnancy and child health outcome

We conducted a follow up of the children in Mongolia whose mothers received one of the three doses of vitamin D (600, 2000, or 4000 IU daily) during pregnancy as part of the randomized, double-blind, clinical trial of vitamin D supplementation to determine their impact on child health to two years. In the parental trial, 119 pregnant women were assigned to 600 IU/day, 121 were assigned 2000 IU/day, and 120 were assigned 4000 IU/day starting at 12–16 weeks’ gestation and continuing throughout pregnancy. At baseline, maternal serum 25(OH)D concentrations were similar across arms; 91 % were 50 nmol/l. As expected, there was a dose-response association between the amount of vitamin D consumed (600, 2000, or 4000 IU daily) and maternal 25(OH)D levels at the end of the intervention. Total 311 children of 311 mothers were followed for 2 years to evaluate health outcomes. We determined the child's health outcomes (rickets, respiratory disease [pneumonia, asthma], and diarrhea/vomiting) using a questionnaire and physical examination (3, 6, and 24 months of age). Low levels of mothers’ serum 25(OH)D during pregnancy increased the risk of developing rickets, respiratory illness, and other diseases in children during the early childhood period. Rickets was diagnosed in 15.6 % of children of women who received 600 IU of vitamin D during pregnancy, which was higher than in other vitamin D groups. Children in the group whose mothers received low doses of vitamin D (600 IU/day) had a greater probability of developing respiratory diseases compared to the other groups: pneumonia was diagnosed in n = 36 (35.0 %) which was significantly higher than the group receiving vitamin D 4000 IU/day (n = 34 (31.5 %) p = 0.048). In the group whose pregnant mother consumed 600 IU/day of vitamin D, the risk of child pneumonia was ∼ 2 times higher than in the group who consumed 4000 IU/day (OR=1.99, 95 % CI: 1.01–3.90). The incidence of diarrhea and vomiting in children was 12.1 % lower in the 2000 IU/day group and 13.1 % lower in the 4000 IU/day group compared with the 600 IU/day group (p = 0.051). The offspring of pregnant women who regularly used vitamin D at doses above 600 IU/day had lower respiratory disease, rickets, and diarrheal risks at 2 years.

Birth weight and large for gestational age trends in offspring of pregnant women with gestational diabetes mellitus in southern China, 2012-2021.

With increasing prevalence of gestational diabetes mellitus (GDM) and changing management of GDM in pregnancy, it is imperative to understand the evolution of its current outcomes. The present study aimed to explore whether birth weight and large for gestational age (LGA) trends in women with GDM have changed over time in southern China. In this hospital-based retrospective study, all singleton live births for the period 2012 to 2021 were collected from the Guangdong Women and Children Hospital, China. GDM was diagnosed following the criteria of the International Association of Diabetes and Pregnancy Study Group. The cutoff points for defining LGA (>90th centile) at birth based on INTERGROWTH-21st gender-specific standards. Linear regression was used to evaluate trends for birth weight over the years. Logistic regression analysis was used to determine the odds ratios (ORs) of LGA between women with GDM and those without GDM. Data from 115097 women with singleton live births were included. The total prevalence of GDM was 16.8%. GDM prevalence varied across different years, with the lowest prevalence in 2014 (15.0%) and the highest prevalence in 2021 (19.2%). The mean birth weight displayed decrease in women with GDM from 3.224kg in 2012 to 3.134kg in 2021, and the z score for mean birth weight decreased from 0.230 to -0.037 (P for trend < 0.001). Among women with GDM, the prevalence of macrosomia and LGA reduced significantly during the study period (from 5.1% to 3.0% in macrosomia and from 11.8% to 7.7% in LGA, respectively). Compared to women without GDM, women with GDM had 1.30 (95% CI: 1.23 - 1.38) times odds for LGA, and the ORs remained stable over the study period. Among offspring of women with GDM, there are decreased trends of birth weight in parallel with reductions in LGA prevalence between 2012 and 2021. However, the risk of LGA in women with GDM remains stable at relatively high level over the 10-year period, and efforts are still needed to address regarding causes and effective intervention strategies.

Associations of Maternal Fructosamine before Delivery in Gestational Diabetes Mellitus Pregnancies with Neonatal Glucometabolic Disorders.

The offspring of pregnant women with gestational diabetes mellitus (GDM) are vulnerable to be glucometabolic disorders. However, to date, few current studies focused on the associations of maternal accumulated glucose exposure before delivery with neonatal glucometabolic disorders and large for gestational age (LGA) infants. This study is aimed at exploring the associations of maternal fructosamine (FMN) before delivery in GDM pregnant women with neonatal glucometabolic disorders in the first 3 days of life and LGA infants. The study subjects were the GDM pregnant women, who gave birth in our hospital from September 1, 2018 to January 31, 2021, and their newborns. The maternal FMN adjusted by serum albumin (FMNALB) before delivery was selected as exposure factors. A multivariate logistical regression model was used to calculate the odds ratios (OR) for neonatal glucometabolic disorders, hypoglycemia needing intervention (<2.6 mmol/L), and glucose intolerance (>7.0 mmol/L) in the first 3 days and LGA infants. In GDM pregnant women, the newborns in the maternal FMNALB ≥ 75th percentile (≥5.89 mmol/g) group had higher risks in neonatal glucometabolic disorders (aOR 2.50, 95% CI 1.34-4.65, P = 0.004) and hypoglycemia (aOR 2.18, 95% CI 1.16-4.10, P = 0.016). However, FMNALB ≥ 75th percentile seemed to be not predictive of the glucose intolerance (aOR 1.76, 95% CI 0.82-3.79, P = 0.149) and LGA (aOR 1.56, 95% CI 0.81-3.02, P = 0.185). Further, in the sensitivity analysis, the newborns in the maternal FMNALB ≥ 90th percentile (≥6.40 mmol/g) group also had higher risks in neonatal glucometabolic disorders (aOR 5.70, 95% CI 2.18-14.89, P < 0.001) and hypoglycemia (aOR 3.72, 95% CI 1.48-9.31, P = 0.005). The maternal FMNALB before delivery in GDM pregnant women was a useful biomarker to identify the offspring with high risk of neonatal glucometabolic disorders. However, the association between maternal FMNALB and the risk of LGA infants was not so strong.

Developmental arsenic exposure impairs cognition, directly targets DNMT3A, and reduces DNA methylation.

Developmental arsenic exposure has been associated with cognitive deficits in epidemiological studies, but the underlying mechanisms remain poorly understood. Here, we establish a mouse model of developmental arsenic exposure exhibiting deficits of recognition and spatial memory in the offspring. These deficits are associated with genome-wide DNA hypomethylation and abnormal expression of cognition-related genes in the hippocampus. Arsenic atoms directly bind to the cysteine-rich ADD domain of DNA methyltransferase 3A (DNMT3A), triggering ubiquitin- and proteasome-mediated degradation of DNMT3A in different cellular contexts. DNMT3A degradation leads to genome-wide DNA hypomethylation in mouse embryonic fibroblasts but not in non-embryonic cell lines. Treatment with metformin, a first-line antidiabetic agent reported to increase DNA methylation, ameliorates the behavioral deficits and normalizes the aberrant expression of cognition-related genes and DNA methylation in the hippocampus of arsenic-exposed offspring. Our study establishes a DNA hypomethylation effect of developmental arsenic exposure and proposes a potential treatment against cognitive deficits in the offspring of pregnant women in arsenic-contaminated areas.

Maternal Viral Infection in Early Pregnancy and Risk of Congenital Heart Disease in Offspring: A Prospective Cohort Study in Central China.

PurposeTo examine the associations of maternal virus infection in early pregnancy with risk of offspring congenital heart disease (CHD) and its seven common subtypes including atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, Tetralogy of Tallot, pulmonary stenosis, and transposition of the great arteries.Patients and MethodsA prospective cohort study was conducted in Central China. A total of 44,048 pregnant women with singleton pregnancies at 8–14 gestational weeks were finally included and followed to 3 months postpartum. Serum was tested for virus infection including hepatitis B virus (HBV), coxsackievirus-B, human cytomegalovirus (HCMV), herpes simplex virus (HSV), and rubella virus. Multivariable modified Poisson regression models were used to estimate the relative risks (RRs) of all CHDs as well as seven common subtypes of CHD in offspring of pregnant women with different types of virus infection in early pregnancy, adjusting for confounders identified by directed acyclic graphs.ResultsAt the end of follow-up, 564 births were diagnosed with CHD. Multivariable analyses showed that the presence of maternal viral infection in early pregnancy was independently associated with increased risks of CHD in offspring, with an adjusted relative risk of 2.21 (95% CI: 1.66–2.95) for HBV infection, 2.21 (95% CI: 1.63–3.00) for coxsackievirus-B infection, 3.12 (95% CI: 2.44–3.98) for HCMV infection, and 2.62 (95% CI: 1.95–3.51) for rubella virus infection. More specifically, the offspring of pregnant women with HCMV infection had the highest increased risk of patent ductus arteriosus (RR=10.50, 95% CI: 6.24–17.66). These findings persisted in analyses that were further adjusted for the other virus of interest in this study.ConclusionOur study proposed evidence that maternal virus infection in early pregnancy, including HBV, coxsackievirus-B, HCMV, and rubella virus, was implicated in CHD, although more studies remain needed to verify the results, especially associations in specific CHD phenotypes.

Abstract 19: Maternal B Cell Depletion Lowers Blood Pressure And Improves Fetal Weights In Offspring In A Rat Model Of Preeclampsia

Preeclampsia (PE), new onset hypertension during pregnancy, is the leading cause of death and morbidity for the mother and low birth weight in offspring. PE women have activated B cells producing agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA). We have shown Rituximab (R), used clinically for B cell depletion, lowers mean arterial pressure (MAP), B cells, and AT1-AA in the RUPP rat model of PE. Clinical studies show no untoward effects on offspring of pregnant women maintained on R for treating lymphoma, however, R is not used during PE therefore, effects of maternal B cell depletion on offspring survival and growth in response to placental ischemia is unknown. We hypothesize that R will deplete maternal B cells in RUPP rats without worsening the effect of placental ischemia on pup growth and survival. To test this hypothesis, R (250 mcg/kg) was given on gestation day (GD) 14 via mini-osmotic pump. On GD 19 B cells were measured by flow cytometry, and MAP and pup weights were recorded. A separate group of dams were allowed to deliver, pup weights were recorded within 12 hours and weekly until 16 weeks, and B cells were analyzed. A one-way ANOVA was used for statistical analysis. MAP increased in RUPP 123±2 (n=19, p&lt;0.05) compared to NP controls 101±1 (n=18) and was 106±3 mmHg in RUPP+R (n=8, p&lt;0.05). On GD19, maternal circulating B cells were 16±2 % (n=14) in RUPPs, 8±2 % in NP rats, (n=7, p&lt;0.05), and 5.5±1% gate in RUPP+R (n=5, p&lt;0.05). RUPP male and female offspring were smaller 5.11±0.23 g, 5.19±0.14 g (n=4, n=4) at birth than NP offspring 6.09±0.15 g, 5.87±0.12 g (n=6, p&lt;0.05; n=6, p&lt;0.05) or RUPP+R offspring 5.75±0.24 g, 5.36±0.28 g (n=6, p=0.11; n=6, p=0.67). At 12 weeks, male and female RUPP offspring had elevated circulating B cells (21±3, 20±1 % (n=6; n=9)) compared to NP (1±0.23, 1.6±0.06 % (n=4, p&lt;0.05; n=3, p&lt;0.04)) which was normalized in RUPP+R offspring (0.4±0.1, 0.3±0.03 % gate (n=3, p&lt;0.05; n=8, p&lt;0.05)). At 16 weeks, B cells were comparable in male offspring from NP (0.78±0.09 % (n=10)) and RUPP+R rats (0.80±0.04 % gate (n=3)). Our findings indicate that R lowers maternal circulating B cells and MAP in RUPP rats and improves fetal weight and circulating B cells, indicating that R does not worsen adverse fetal outcomes in response to placental ischemia.

Possible risk of fetal development of autism in pregnant women infected by SARS-CoV-2

Introduction. In March 2020, the World Health Organization (WHO) announced the emergence of a global pandemic, COVID-19. A disease triggered by the new coronavirus infection (SARS-CoV-2). More recent findings indicate that the gestational period makes the mother and her offspring more susceptible to the new coronavirus and the rapid progression to the critical stage of the disease. The maternal organism presents a certain degree of immunological and cardiorespiratory deficiency due to physiological adaptations to the gestational period and, consequently, if affected by prenatal infections caused by viruses, they lead to an exacerbated Maternal Immune Activation (MIA), thus contributing to alterations in maternal-fetal neurogenesis, fetal myelinization, and is directly involved in the pathogenesis of neurodevelopmental disorders in the offspring, especially autism. Objective. This study hypothesizes that maternal COVID-19 infections during pregnancy are a potential risk for the offspring to develop Autism Spectrum Disorder. Conclusion. The exposure to viral infectious agents during the gestational period leads to exacerbated maternal immune activation. It contributes to alterations in maternal-fetal neurogenesis and is directly involved in the pathogenesis of neurodevelopmental disorders, being correlated to the predisposition to affective and psychiatric disorders in the offspring. Therefore, greater attention should be given to the offspring of pregnant women infected by COVID-19, since prenatal infectious processes have a strong correlation with the prevalence of Autistic Spectrum Disorder in the offspring.

Maternal celiac disease and the risk for long-term infectious morbidity of the offspring.

Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease. A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups. During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p=.004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p=.001), and infections of the central nervous system (1% vs. 0.2%; p=.028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR=1.6, 95% CI 1.165-2.357, p=.005). Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring.

Current status of group B Streptococcus infection in neonates: a multicenter prospective study.

To investigate the incidence of maternal group B Streptococcus (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (P<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), P<0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (P<0.05), while adequate IAP was a protective factor (P<0.05) in the offspring of pregnant women with GBS colonization. GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. Citation.

Neonatal Outcomes in the MONEAD Study of Pregnant Women with Epilepsy

To determine whether growth measures at birth differ between offspring of pregnant women with epilepsy and healthy pregnant women. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a National Institutes of Health-funded, prospective, observational, multicenter investigation of pregnancy outcomes for mothers and their infants. Between 2012 and 2016, pregnant women with epilepsy and healthy pregnant women were enrolled at 20 US epilepsy centers. Pregnant women with epilepsy were exposed to various antiepileptic drugs. The main outcome measure was small for gestational age at birth. Principal univariate and multivariate analyses compared outcomes between pregnant women with epilepsy and healthy pregnant women. Secondary analyses focused on outcomes among mothers receiving different antiepileptic drug therapies. In total, 345 infants were born to 331 pregnant women with epilepsy and 106 infants were born to 102 healthy pregnant women. No differences were seen between infants born to pregnant women with epilepsy vs healthy pregnant women in preterm births, major congenital malformations, 5-minute Apgar <6, special care nursery or neonatal intensive care unit admission, gestational age, or any growth measure. There was no difference in the rates of small for gestational age status among infants born to pregnant women with epilepsy vs healthy pregnant women; however, infants born to mothers receiving topiramate had lower birth weight z scores and lamotrigine higher birth weight z scores compared with other monotherapies. The greatest rate of special care nursery or neonatal intensive care unit admission was observed among those on oxcarbazepine monotherapy. Maternal treatment with antiepileptic drugs, overall, appears unassociated with adverse early neonatal outcomes. However, specific monotherapies appear to affect fetal growth with, on average, the greatest reduction in birth weight z score observed among infants born to pregnant women with epilepsy exposed to topiramate monotherapy.

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta-Analyses.

This article reviewed the results of 21 recent meta-analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta-analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta-analysis, selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta-analyses that met the inclusion criteria. Most of the meta-analyses reported that compared to non-users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta-analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta-analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.

Ophthalmic Pathology in the Offspring of Pregnant Women with Gestational Diabetes Mellitus.

Gestational diabetes (GD) occurs in 5.8% to 25.1% of pregnant women. This disorder has been linked with intrauterine growth delays, congenital anomalies, and neurobehavioral disorders following birth. As to ophthalmological effects, changes in macular thickness and hypoplasia of the upper quadrant of the papilla have been described. To investigate whether GD has an effect on ophthalmological development in the children born of mothers with this condition. Observational study carried out in children seen in the ophthalmological outpatient clinic of a pediatric hospital in Barcelona (Spain) between January 2011 and December 2015. Participants were ultimately divided into two groups, a study group whose mothers had GD managed either by insulin or diet (GD group) and a control group of children with non-diabetic mothers. Pregestational diabetes cases, were excluded. Complete information was collected on the children's refraction status, ophthalmological disease, and congenital malformations. Data were compiled on 350 children (229 children born of mothers with GD-186 managed with diet vs 43, with insulin- and 121 controls). The prevalence of amblyopia and strabismus was similar between the groups, but children of mothers with GD had a three-fold greater probability of having refractive errors than children born to mothers without GD. Hyperopia (14.8% vs. 7.4%) and myopia (3.5% vs 0%) were found to be significantly more prevalent in children born of mothers with GD than in the controls (p = 0.027 in both groups).The prevalence of astigmatism was similar in both groups (1.7% vs 0.8%). Refractive errors are more common in children born of mothers with GD. These conditions are easily managed, but if they are not detected, they can lead to amblyopia or accommodative strabismus, interfere with acquisition of fine motor skills, and lead to learning problems. Regular ocular examinations would be recommended in these patients.

Complications of Hyperemesis Gravidarum; A Disease of Both Mother and Fetus, Review Article

Hyperemesis Gravidarum (HG) is the most severe form of nausea and vomiting during pregnancy and is characterized by severe intractable nausea and vomiting that lead to many maternal and fetal consequences. HG is mainly diagnosed clinically; most of the physicians diagnose it by its typical clinical picture and exclusion of other causes of nausea and vomiting in the pregnant woman. Nausea and vomiting are a disease of high prevalence among pregnant women and it is a common experience affecting 50-90% of all women. It is the most common indication for hospitalization during the first half of pregnancy. HG occurs in only about 0.5-2% of cases but actually, when it occurs it may be associated with morbidity of both mother and fetus. Adequate replacement therapy and weight gain may prevent most of the maternal and fetal consequences. Pregnant women with HG may suffer marked psychosocial burden. Moreover, the condition may be complicated by electrolyte imbalances, nutritional deficiencies, and Wernicke’s encephalopathy. Other complications include thrombosis, esophageal trauma, cerebral vascular spasm, others are related to TPN and central venous lines. Besides, recurrence of HG in subsequent pregnancies may occur. Offspring of pregnant women with HG may suffer long-term conditions which include high serum cortisol, decreasing insulin sensitivity, high risk of mood and psychiatric problems. Studies showed no significant increase in the incidence of congenital anomalies among these neonates versus the control group. Regarding cancer, the large Scandinavian study found no association between HG and incidence of 12 types of childhood malignancies, only increased the incidence of lymphoma and testicular tumor was found which need further studies to confirm this causal relation. Besides, higher incidence of preterm labor, placental abruption, preeclampsia and small for gestational age were found in these patients. Further studies are needed to determine long-term maternal complications and to study long-term effect of HG on the mental and physiological status of offspring of HG mothers during adulthood.

Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

BackgroundThe World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality.Methods and FindingsThe study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose–response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research.ConclusionsRapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.

The Strange Case of Smoking and Schizophrenia—The Epidemiology Detectives Are on the Trail

The Strange Case of Smoking and Schizophrenia—The Epidemiology Detectives Are on the Trail

&lt;b&gt;Mutagenic effect of contaminated soil on the offspring of exposed rats

This study aimed to measure irreversible DNA damage in the offspring of rats exposed to contaminated soil. Bone marrow cells were removed from the femurs of the offspring of rats that were exposed to contaminated soil via gavage during three different periods: 21 days prior to detection of pregnancy, during pregnancy and 21 days after birth, during the lactation period. For each group, we also had a control group under the same experimental conditions but exposed to uncontaminated soil. The results showed that pups borne of rats exposed to contaminated soil had an increase in the number of micronuclei in the different exposure groups compared with their respective control groups. This suggests a potential risk of mutagenic damage to the offspring of pregnant women who live at the sampling site.

Optimizing Cardiovascular Health Across the Life Course.

Optimizing Cardiovascular Health Across the Life Course.

Birth Outcomes of Children Born to Women with Rheumatoid Arthritis

The aim of the study was to estimate the possible risk of adverse birth outcomes of children born to mothers with rheumatoid arthritis (RA). The dataset of large population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities from 1980-1996 was evaluated including 22,843 cases with congenital abnormalities and 38,151 matched controls without any defect. 36 cases (0.16%) had mothers with RA, while 68 controls (0.18%) were born to mothers without RA (OR=0.9, 95% CI=0.3-1.6). A higher risk for congenital abnormalities in the offspring of pregnant women with RA was not found. In fact there was a larger mean birth weight in the newborns without any defect of mothers with RA and it was associated with a somewhat lower rate of low birth weight. RA seems to have a beneficial effect not only for pregnant women but for their foetuses as well.

Transgenerational Inheritance in the Offspring of Pregnant Women with Metabolic Syndrome

Currently, it is well-known that changes in the maternal metabolic status induce changes in the intrauterine environment and modify the metabolic status of the fetuses, playing a key role in the growth, life-time fitness/obesity and probability of appearance of metabolic disorders in the offspring. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations either exposed (multigenerational exposure) or unexposed (intergenerational or transgenerational inheritance) to such metabolic defies, perpetuating the problem. Thus, having in mind the impact on worldwide public health, the present review outlines, based on results of translational animal research and clinical human studies, the mechanisms, pathways and practical implications involved in the transgenerational inheritance of the metabolic syndrome.