Sister-chromatid exchanges in operating room personnel.

Sister-chromatid exchange (SCE) analysis was carried out in 67 operating room personnel (anaesthetists M.D.; anaesthesia nurses and anaesthesia unit technicians) exposed to waste anaesthetic gases such as halothane, nitrous oxide and isoflurane and in 50 healthy unexposed controls. The SCE frequencies were increased significantly in operating room personnel as compared to controls. A significant increase in SCEs was found in non-smoking operating room personnel as compared to non-smoking controls. This study supports the existence of an association between occupational exposure to mutagens and an increase in SCEs in lymphocytes.     

The effects of prenatal exposure to Ramadan on stature during childhood and adolescence: Evidence from the Indonesian Family Life Survey

Many pregnant Muslim women fast during the Muslim holy month of Ramadan. A number of studies have reported negative life outcomes in adulthood for children who were prenatally exposed to Ramadan. However, other studies document minimal to no impact on neonatal indicators. Using data from the Indonesian Family Life Survey consisting of 45,246 observations of 21,723 children born to 9771 mothers, we contribute to the current discussion on prenatal exposure to Ramadan by examining the effects on stature (height-for-age Z-scores, weight-for-age Z-scores, and body-mass-index-for-age Z-scores: HAZ, WAZ, and BAZ, respectively) from early childhood to late adolescence (0–19 years of age). We introduce an objective mother’s religiosity indicator to improve the intention-to-treat estimations. Children were classified into three groups based on their mother’s religion-religiosity: religious Muslims, less-religious Muslims, and non-Muslims. Using cluster-robust mother fixed-effects, we found negative effects on stature for children born to religious Muslim mothers. The effects were age-dependent and timing-sensitive. For example, children born to religious Muslim mothers were shorter in late adolescence (15–19 years of age) compared to their unexposed siblings if they were prenatally exposed in the first trimester of pregnancy (HAZ difference = −0.105 SD; p-val. <0.05). Interestingly, we found positive effects on stature for exposed less-religious Muslim children that peak in early adolescence (10–14 years of age) and negative effects on stature for exposed non-Muslim children that occur only in early childhood (0–4 years of age). We nuance our discussion of health and socioeconomic factors to explain these surprising results.     

Clinical and Serological Assessment of Children Exposed in Utero to Confirmed Maternal Rubella

As a result of the work of the Public Health Laboratory Service Working Party on Rubella (1970) it was possible to examine the children of 60 susceptible women who were in contact with rubella during their pregnancy and who subsequently showed serological evidence of the infection, despite immunoglobulin prophylaxis. When the children were assessed between 8 months and 4 years 8 months of age a blood sample was also taken and tested for rubella antibodies so that a retrospective diagnosis of congenital rubella infection could be made. Only 19% of children exposed to subclinical maternal rubella showed evidence of intrauterine infection compared with 53% of those born to mothers who had clinical rubella. One of the 26 children exposed to subclinical maternal infection had a rubella defect, compared with 9 of the 34 children exposed to clinical maternal rubella.     

Weight growth in infants born to mothers who smoked during pregnancy.

OBJECTIVE--To determine whether maternal smoking during pregnancy causes impairment in growth after birth. DESIGN--Longitudinal study. SETTING--Six medical university centres of six towns of north, central, and south Italy. SUBJECTS--12,987 babies (10,238 born from non-smoking mothers, 2276 from mothers smoking one to nine cigarettes a day, and 473 from mothers smoking > or = 10 cigarettes a day) entered the study. MAIN OUTCOME MEASURES--Difference in weight gain between children born to smoking mothers and those born to non-smoking mothers. Weight was measured at birth and at 3 and 6 months of age. Maternal smoking habit was derived from interview on third or fourth day after delivery. RESULTS--Compared with children born to mothers who did not smoke during pregnancy, the birth weights of children born to mothers who smoked up to nine cigarettes a day were 88 g (girls) and 107 g (boys) lower; in children born to mothers who smoked > or = 10 cigarettes a day weights were 168 g and 247 g lower. At six months of age for the first group the mean weight for girls was 9 g (95% confidence interval -47 g to 65 g) higher and for boys 64 g (-118 g to -10 g) lower than that of children born to mothers who did not smoke. The corresponding figures for the second group were 28 g (-141 g to 85 g) lower for girls and 24 g (-136 g to 88 g) lower for boys. CONCLUSIONS--The deficits of weight at birth in children born to mothers who smoked during pregnancy are overcome by 6 months of age. These deficits are probably not permanent when smoking habit during pregnancy is not associated with other unfavourable variables (such as lower socioeconomic class).     

Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight

Background

It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population–based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.

Methodology/Principal Findings

We followed 65,212 children born in Denmark from 1970–1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08–2.61) at 12 years of age and 1.63 (95% CI 1.00–2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71–6.42 at age 12, and OR 2.31, 95% CI 1.08–4.97 at age 13).

Conclusions/Significance

Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.     

Prenatal Exposure to Maternal Bereavement and Childbirths in the Offspring: A Population-Based Cohort Study

IntroductionThe decline in birth rates is a concern in public health. Fertility is partly determined before birth by the intrauterine environment and prenatal exposure to maternal stress could, through hormonal disturbance, play a role. There has been such evidence from animal studies but not from humans. We aimed to examine the association between prenatal stress due to maternal bereavement following the death of a relative and childbirths in the offspring.ResultsA total of 4,121,596 subjects were followed-up until up to 41 years of age. Of these subjects, 93,635 (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of having at least one child for exposed males and females were 0.98 [0.96–1.01] and 1.01 [0.98–1.03], respectively. We found a slightly reduced probability of having children in females born to mothers who lost a parent with HR = 0.97 [0.94–0.99] and increased probability in females born to mothers who lost another child (HR = 1.09 [1.04–1.14]), the spouse (HR = 1.29 [1.12–1.48]) or a sibling (HR = 1.13 [1.01–1.27]).ConclusionsOur results suggested no overall association between prenatal exposure to maternal stress and having a child in early adulthood but a longer time of follow-up is necessary in order to reach a firmer conclusion.     

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

BackgroundThe 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 findingsWe 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%.ConclusionsA 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.     

Desert locust swarms and child health

This study evaluates how in-utero exposure to an insect pest invasion, particularly, the outbreak of desert locust swarms, affects early childhood health in Africa and Asia over the past three decades (1990–2018). Employing the difference-in-differences model, we find that children being prenatally exposed to the outbreak have their height-for-age, weight-for-height, and weight-for-age z-scores lower by 0.159, 0.148, and 0.155 standard deviations, respectively, compared to unexposed children. Our heterogeneity analyses show that the health setbacks disproportionately fall on children of disadvantaged backgrounds, i.e., those born to lower-educated mothers, poorer mothers, and rural mothers. To the extent that poor health in early life exerts long-lasting irreversible consequences over the life cycle, the study calls for effective measures to minimize the pernicious effects of the desert locust swarm outbreak.     

Retrospective study of maternal HIV-1 and HIV-2 infections and child survival in Abidjan,C?te d'Ivoire.

OBJECTIVES--To compare the effects of maternal HIV-1 and HIV-2 infections on outcome of pregnancy, infant mortality, and child survival, and to measure serological concordance between mothers and children. DESIGN--Retrospective cohort study with cross sectional study of concordance for HIV antibodies. SETTING--Hospital, tuberculosis clinic, and maternal and child health centre in Abidjan, Côte d''Ivoire, west Africa. SUBJECTS--986 women who had had a total of 2758 pregnancies since 1980. The last born children of 194 of these women. MAIN OUTCOME MEASURES--Pregnancy outcomes; mortality for all children born since 1980; and outcome for last born children. Serological concordance between mothers and last born children. RESULTS--Women with HIV-1 and HIV-2 infections had higher rates of spontaneous abortion and stillbirth than uninfected women (86/769 in HIV-1 positive women, 48/421 in HIV-2 positive, 31/234 in dually reactive, and 96/1131 in uninfected). Compared with children born to uninfected mothers (mortality 10.3%), greater proportions of children of HIV-1 positive (20.6%) and dually reactive (20.3%) mothers had died; mortality in children of HIV-2 infected women (13.1%) was not significantly increased. Infant mortalities for the last born children of HIV-1 positive, dually reactive, HIV-2 positive, and seronegative women were, respectively, 133, 82, 32, and 40 per 1000 live births. Nine of 77 last born children of HIV-1 positive mothers were concordantly seropositive compared with none of 21 children of HIV-2 infected mothers. CONCLUSIONS--Maternal HIV-2 infection has less influence on child survival than infection with HIV-1, probably because of a lower vertical transmission rate.     

Maternal exposure to predation risk decreases offspring antipredator behaviour and survival in threespined stickleback

1. Adaptive maternal programming occurs when mothers alter their offspring's phenotype in response to environmental information such that it improves offspring fitness. When a mother's environment is predictive of the conditions her offspring are likely to encounter, such transgenerational plasticity enables offspring to be better-prepared for this particular environment. However, maternal effects can also have deleterious effects on fitness.2. Here, we test whether female threespined stickleback fish exposed to predation risk adaptively prepare their offspring to cope with predators. We either exposed gravid females to a model predator or not, and compared their offspring's antipredator behaviour and survival when alone with a live predator. Importantly, we measured offspring behaviour and survival in the face of the same type of predator that threatened their mothers (Northern pike).3. We did not find evidence for adaptive maternal programming; offspring of predator-exposed mothers were less likely to orient to the predator than offspring from unexposed mothers. In our predation assay, orienting to the predator was an effective antipredator behaviour and those that oriented, survived for longer.4. In addition, offspring from predator-exposed mothers were caught more quickly by the predator on average than offspring from unexposed mothers. The difference in antipredator behaviour between the maternal predator-exposure treatments offers a potential behavioural mechanism contributing to the difference in survival between maternal treatments.5. However, the strength and direction of the maternal effect on offspring survival depended on offspring size. Specifically, the larger the offspring from predator-exposed mothers, the more vulnerable they were to predation compared to offspring from unexposed mothers.6. Our results suggest that the predation risk perceived by mothers can have long-term behavioural and fitness consequences for offspring in response to the same predator. These stress-mediated maternal effects can have nonadaptive consequences for offspring when they find themselves alone with a predator. In addition, complex interactions between such maternal effects and offspring traits such as size can influence our conclusions about the adaptive nature of maternal effects.     

Maternal exposure to predator scents: offspring phenotypic adjustment and dispersal

Predation is a strong selective pressure generating morphological, physiological and behavioural responses in organisms. As predation risk is often higher during juvenile stages, antipredator defences expressed early in life are paramount to survival. Maternal effects are an efficient pathway to produce such defences. We investigated whether maternal exposure to predator cues during gestation affected juvenile morphology, behaviour and dispersal in common lizards (Zootoca vivipara). We exposed 21 gravid females to saurophagous snake cues for one month while 21 females remained unexposed (i.e. control). We measured body size, preferred temperature and activity level for each neonate, and released them into semi-natural enclosures connected to corridors in order to measure dispersal. Offspring from exposed mothers grew longer tails, selected lower temperatures and dispersed thrice more than offspring from unexposed mothers. Because both tail autotomy and altered thermoregulatory behaviour are common antipredator tactics in lizards, these results suggest that mothers adjusted offspring phenotype to risky natal environments (tail length) or increased risk avoidance (dispersal). Although maternal effects can be passive consequences of maternal stress, our results strongly militate for them to be an adaptive antipredator response that may increase offspring survival prospects.     

Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women

BACKGROUND: Previous studies suggest that trichloroethylene (TCE) is a selective cardiac teratogen. We tested the hypothesis that the odds of maternal residence close to TCE-emitting sites would be greater among infants with congenital heart defects (CHDs) than among infants without CHDs. METHODS: We conducted a case-control study of 4025 infants, identified from hospital and birth records, born from 1997 to 1999 to Milwaukee, Wisconsin mothers. A geographic information system was used to calculate distances between maternal residences and TCE sites. We used classification tree analysis to determine appropriate values by which to dichotomously categorize mothers by TCE exposure (exposed: residence within 1.32 miles of at least one TCE site) and age (older: >/=38 years), and logistic regression to test for CHD risk factors. RESULTS: The proportion of mothers who were both older and had presumed TCE exposure was more than six-fold greater among case infants than among control infants (3.3% [8/245] versus 0.5% [19/3780]). When adjusted for other variables, CHD risk was over three-fold greater among infants of older, exposed mothers compared to infants of older, nonexposed mothers (adjusted OR, 3.2; 95% CI, 1.2-8.7). Older maternal age, alcohol use, chronic hypertension, and preexisting diabetes were each associated with CHDs (adjusted ORs, 1.9, 2.1, 2.8, 4.1; 95% CIs, 1.1-3.5, 1.1-4.2, 1.2-6.7, 1.5-11.2, respectively), but residence close to TCE sites alone was not. CONCLUSIONS: Our findings suggest that maternal age and TCE exposure interact to increase CHD risk, although the mechanism by which this occurs is unknown. A prospective study is underway to confirm this finding.     

Prenatal epoxiconazole exposure effects on rat postnatal development

Although some studies have pointed out to embryo/fetal toxicity, knowledge about the potential toxicity of the fungicide epoxiconazole is still limited. Once the results of these previous studies have raised some concern, this study studied the effects of epoxiconazole maternal exposure on the physical endpoints in the development of rat pups. To accomplish that, the effects of epoxiconazole (50.0, 100.0, and 150.0 mg/kg) were examined when rats were exposed at two different developmental stages: during the first 6 days of pregnancy or in the organogenesis period (6-15 days). After parturition, pups were tested for growth and maturational milestones. Maternal exposure to the fungicide, independently of phase, resulted in significantly early mean time to vaginal opening and delayed time to testes descent in pups. Weight gain rate in pups and their mothers was not affected for the tested exposure period. The findings of this study emphasize that epoxiconazole maternal exposure may lead to alterations in developmental patterns in nursing pups, consistent with the known influence of epoxiconazole on steroid hormone synthesis.     

Prenatal exposure to bereavement and type-2 diabetes: a danish longitudinal population based study

Background

The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.

Methods

We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1^st 1979 through December 31^st 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child’s birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents’ history of diabetes at the time of pregnancy.

Results

We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01–1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94–2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15–3.76).

Conclusions

Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.     

Early Neurodevelopment and Self-Reported Adolescent Symptoms of Depression and Anxiety in a National Canadian Cohort Study

Objective

Little is known about the mental health outcomes of young children who experience developmental delay. The objective of this study was to assess whether delay in attaining developmental milestones was related to depressive and anxious symptoms in adolescence.

Method

The sample included 3508 Canadian children who participated in a nationally representative prospective cohort study. The person most knowledgeable about the child reported on attainment of developmental milestones spanning several developmental domains at ages 2–3. The children were followed into adolescence and self-reported depressive and anxious symptoms were used from adolescents ages 12–13. An overall assessment of developmental milestones as well as a supplementary analysis of specific categories of developmental milestones was conducted.

Results

Cohort members who displayed delayed developmental milestones in early childhood were more likely to experience higher levels of depressive and anxious symptoms as adolescents. However, there was no interaction between delayed developmental milestones and stressful life events. In the supplementary analysis, two developmental domains (self-care and speech/communication) were associated with higher levels of depressive and anxious symptoms in adolescence.

Conclusion

Delay in attainment of early developmental milestones is significantly associated with adolescent depressive and anxious symptoms.     

Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study

Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross‐sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.     

Maternal predator-exposure has lifelong consequences for offspring learning in threespined sticklebacks

Learning is an important form of phenotypic plasticity that allows organisms to adjust their behaviour to the environment. An individual''s learning performance can be affected by its mother''s environment. For example, mothers exposed to stressors, such as restraint and forced swimming, often produce offspring with impaired learning performance. However, it is unclear whether there are maternal effects on offspring learning when mothers are exposed to ecologically relevant stressors, such as predation risk. Here, we examined whether maternal predator-exposure affects adult offsprings’ learning of a discrimination task in threespined sticklebacks (Gasterosteus aculeatus). Mothers were either repeatedly chased by a model predator (predator-exposed) or not (unexposed) while producing eggs. Performance of adult offspring from predator-exposed and unexposed mothers was assessed in a discrimination task that paired a particular coloured chamber with a food reward. Following training, all offspring learned the colour-association, but offspring of predator-exposed mothers located the food reward more slowly than offspring of unexposed mothers. This pattern was not driven by initial differences in exploratory behaviour. These results demonstrate that an ecologically relevant stressor (predation risk) can induce maternal effects on offspring learning, and perhaps behavioural plasticity more generally, that last into adulthood.     

Mortality and Health Outcomes of HIV-Exposed and Unexposed Children in a PMTCT Cohort in Malawi

Background

Mortality and morbidity among HIV-exposed children are thought to be high in Malawi. We sought to determine mortality and health outcomes of HIV-exposed and unexposed infants within a PMTCT program.

Method

Data were collected as part of a retrospective cohort study in Zomba District, Malawi. HIV-infected mothers were identified via antenatal, delivery and postpartum records with a delivery date 18–20 months prior; the next registered HIV-uninfected mother was identified as a control. By interview and health record review, data on socio-demographic characteristics, service uptake, and health outcomes were collected. HIV-testing was offered to all exposed children.

Results

173 HIV-infected and 214 uninfected mothers were included. 4 stillbirths (1.0%) occurred; among the 383 livebirths, 41 (10.7%) children died by 20 months (32 (18.7%) HIV-exposed and 9 unexposed children (4.3%; p<0.0001)). Risk factors for child death included: HIV-exposure [adjOR2.9(95%CI 1.1–7.2)], low birthweight [adjOR2.5(1.0–6.3)], previous child death (adjOR25.1(6.5–97.5)] and maternal death [adjOR5.3(11.4–20.5)]. At 20 months, HIV-infected children had significantly poorer health outcomes than HIV-unexposed children and HIV-exposed but uninfected children (HIV-EU), including: hospital admissions, delayed development, undernutrition and restrictions in function (Lansky scale); no significant differences were seen between HIV-EU and HIV-unexposed children. Overall, no difference was seen at 20 months among HIV-infected, HIV-EU and HIV-unexposed groups in Z-scores (%<−2.0) for weight, height and BMI. Risk factors for poor functional health status at 20 months included: HIV-infection [adjOR8.9(2.4–32.6)], maternal illness [adjOR2.8(1.5–5.0)] and low birthweight [adjOR2.0(1.0–4.1)].

Conclusion

Child mortality remains high within this context and could be reduced through more effective PMTCT including prioritizing the treatment of maternal HIV infection to address the effect of maternal health and survival on infant health and survival. HIV-infected children demonstrated developmental delays, functional health and nutritional deficits that underscore the need for increased uptake of early infant diagnosis and institution of ART for all infected infants.