Paracetamol exposure in utero or during infancy: no increase in asthma

The increasing incidence of asthma among children, and the increase in paracetamol exposure, suggested a possible link between the two. Most relevant data concern wheezing episodes in infants rather than asthma. About 20 epidemiological studies have been published. Due to numerous biases, particularly the possible link between the use of paracetamol and respiratory disorders that preceded the diagnosis of asthma, these studies fail to show that paracetamol exposure in utero or during the first year of life causes persistent asthma. These data do not challenge the known harm-benefit balance of paracetamol during pregnancy and infancy. Paracetamol remains the analgesic and antipyretic drug of choice in both situations.     

In utero exposure to itraconazole during different gestational periods of rats

The present study aimed to investigate the teratogenic and genotoxic effects of itraconazole administered orally to pregnant rats on gestation days 1–7 (implantation), 8–14 (organogenesis) and 14–20 (fetal developmental period) at doses 75, 100 or 150?mg/kg b.wt. The results indicated that itraconazole had embryolethal effect when administered at a dose of 150?mg/kg b.wt throughout implantation and organogenesis periods as well as at 100?mg/kg b.wt during implantation period. Itraconazole elevated the teratogenicity when administrated at a dose of 100?mg/kg b.wt during organogenesis period, the most prominent abnormalities were abdominal hernia, protruding tongue, exencephaly, incompletely ossified, unossified or missing skull bones (mostly frontal, parietal and interparietal), abnormal vertebrae and fused and supernumerary ribs. However, minimal adverse effects were observed at doses given during the fetal developmental period. Itraconazole increased DNA damage of fetal osteocytes via significant increase in the measured comet parameters in all the treated groups, indicating that itraconazole severely affects fetal genetic material.     

Neurological disorders after zidovudine exposure in utero

(1) New cases of mitochondrial disorders have been described in French children exposed to zidovudine in utero. Despite this, zidovudine remains the reference prophylaxis for mother-child HIV transmission.     

Psychological consequences of DES exposure in utero

Between the 1950s and the late 1970s, millions of women worldwide took diethylstilbestrol (DES) during pregnancy. It was claimed that DES prevented miscarriage, even though a clinical trial was interrupted in 1953 when an interim analysis showed no beneficial effect in the prevention of miscarriage. In 1971, it emerged that DES exposure in utero was associated with somatic effects in adulthood, including female genital abnormalities with obstetric consequences, vaginal cancer, and male urogenital disorders. This article examines the psychological effects of exposure to DES in utero, based on a review of the literature using the standard Prescrire methodology. In two experimental studies, mice exposed to DES during gestation were found to be more aggressive than unexposed mice. A randomised clinical trial and epidemiological studies have pointed to a risk of psychological disorders during adolescence and adulthood after DES exposure in utero. A placebo-controlled randomised trial of DES was conducted in London in the 1950s but was never published. In the 1980s, a research team recovered some of the original data and obtained information on the adult health status of the persons exposed in utero. Compared to the placebo group, psychological disorders were twice as frequent in the adults who were likely to have been exposed to DES in utero. Three large epidemiological studies were also conducted. One study showed that major depressive episodes were about 1.5 times more frequent in women exposed to DES in utero than in unexposed women; the second showed that exposed women had an episode of major weight loss more often than unexposed women; while the third showed no significant difference between the groups in terms of depressive episodes. Smaller studies also suggest that depressive episodes tend to be more frequent after DES exposure in utero. In practice, these data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly.     

In utero exposure to phthalates and fetal development

The diesters of benzene-1,2-dicarboxylic (phthalic) acid, commonly known as phthalates, are a family of industrial compounds, primarily used as plasticizers in enormous quantities for a variety of industrial uses in the formulation of plastics. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer. These plasticizers are not covalently bound to the polymer and leach out into the environment, thus becoming ubiquitous environmental contaminants. Cumulating evidence points out on the adverse effects of phthalate exposure during intrauterine life. Recently, it has been documented that in utero phthalate exposure is associated with a shorter duration of pregnancy. Phthalates induce and activate a subset of peroxisome proliferator-activated receptors (PPARs) and have an intrinsic pro-inflammatory activity, while some natural PPAR agonists induce cyclooxygenase (COX)-2 expression. To this regard, COX-2 is thought to be overexpressed in chorioamnionitis (CA), a fetal systemic inflammatory response syndrome and a leading cause of preterm birth. An adequate maternal dietary intake of essential fatty acids, well known anti-inflammatory agents, is indispensable to fetal development. Recently, it has been shown that phthalates alter the placental essential fatty acids (EFAs) homeostasis so potentially leading to abnormal fetal development. Likewise, a possible down-regulation of COX-2 by omega-3 fatty acids has been suggested. As a consequence, maternal supplementation with omega 3 during pregnancy could counteract the adverse effects of phthalates exposure in the human fetus. Here, we analyze the existing evidence on the link between antenatal phthalate exposure and abnormal fetal development, as well as on possible therapeutic tools to fight the adverse effect of this exposure.     

Mercury exposure in children: a review

Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage. Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children. Reports of elemental Hg vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Hg for magico-religious purposes in urban communities are also discussed. Studies of inorganic Hg exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Hg exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders.     

Mercury and trace element distribution in organic tissues and regional brain of fetal rat after in utero and weaning exposure to low dose of inorganic mercury

Since it is still absent data about the toxic risk of low dose, especially an environmentally relevant dose of mercury to fetus after their prenatal exposure, this present work was designed to investigate the metabolism of Hg and its effect on the levels of essential trace elements in the organic tissues and the brain regions of infant rats after their exposure to environmentally relevant low dose of Hg(II) during the whole pregnant and weaning period. The pregnant female rats were exposed to a very low dose of 0.2 microg Hg2+/ml (as HgCl2, 12 rats/group) in drinking water from prenatal day 0 continued to postnatal day 20. The contents of Hg and other elements (Cu, K, Mg, Mn, Na, Ca, Co, Fe, Se and Zn) in the liver, kidney, heart, spleen, pancreas and the brain regions (cerebrum, cerebellum, brain stem, hippocampus, thalamus and the remains) of the maternal and their infant rats were determined. The highest Hg contents were found in kidney of both maternal and infant rats. Considering the percentage of Hg accumulation, approximately 52.7%, 38.7%, and 1.66% were found in kidney, liver and brain for maternal rats, respectively, while 23.7%, 48.9% and 15.6% for infant rats. The important findings in this work were that the low dose of inorganic mercury appeared to accumulate in the brain of offspring and more Hg was present in infant brain than in their mother. As in the brain regions, the highest Hg content was present in infant hippocampus and cerebellum, whereas the Hg contents in maternal brains varied not so much. The imbalances of Fe/Cu, Cu/Zn, Zn/Se mass ratios and the molar ratios of Hg over other elements in the Hg-exposed rats were observed.     

Distribution of mercury in guinea pig offspring after in utero exposure to mercury vapor during late gestation

Organ distribution of mercury after in utero mercury vapor exposure was investigated in neonatal guinea pigs. Mother guinea pigs in late gestation were exposed to 0.2–0.3 mg/m³ mercury vapor 2 h per day until giving birth.Mercury concentrations in neonatal brain, lungs, heart, kidneys, plasma and erythrocytes were much lower than those of maternal organs and tissues. Neonatal liver, however, showed a mercury concentration twice as high as maternal liver. Mercury concentration ratios of erythrocytes to plasma in offspring were quite different from those of mothers, being 0.2–0.4 for offspring, and 1.3–3.0 for mothers.These results suggested that mercury vapor metabolism in fetuses was quite different from that in their mothers. This may be due to the different blood circulation, as mercury vapor transferred through the placental barrier would be rapidly oxidized into ionic mercury in fetal liver and accumulated in the organ.The different mercury vapor metabolism may prevent fetal brain, which is rapidly developing, and thus vulnerable, from being exposed to excessive mercury vapor.     

Cocaine exposure in utero: perinatal development and neonatal manifestations--review.

The question of whether cocaine exposure in utero increases the risk of major structural malformations remains controversial. Most animal studies have demonstrated that cocaine can have a teratogenic effect. The ultimate association between cocaine exposure and fetal development must be inferred from human data. The relative effects of cocaine exposure, exposure to other illicit drugs and alcohol and deficient prenatal care are difficult to assess. Little specific information is available about the amount, duration, and timing of cocaine use during the nine months of pregnancy. Unlike the case with many other teratogens, cocaine exposure at any point in pregnancy can result in some abnormality. The extent of damage and the organ involved depend on the particular stage of morphogenesis. A large scale prospective human study is needed to confirm the suggested teratogenic effects. Since it involves an illicit drug such a study is obviously difficult to perform.     

In utero and postnatal vitamin D exposure and allergy risk

Introduction: The epidemic of allergic disease is a public health crisis, particularly for children in developed countries. Recognized effects of vitamin D in immune development have given credence to the hypothesis that changing patterns of human behavior associated with declining sunlight exposure may be linked to the rising immune and inflammatory diseases. Although data to support this are still limited and heterogeneous, vitamin D supplementation in early life is recommended to prevent vitamin D deficiency in many countries, raising important questions around safety and benefit for immune development and implications for allergic risk.

Areas covered: This review article examines the evidence of the impact of in utero and postnatal vitamin D exposure on allergy risk in childhood. Evaluated are relevant studies from 2007 to June 2014.

Expert opinion: Information on the impact of vitamin D on rising rates of allergic diseases is largely based on observational studies with conflicting results. There is an urgent need to conduct well-designed randomized controlled trials to address the significant uncertainty in this field. Additionally, the effects of other potential immunomodulatory factors associated with sun exposure (such as UV light) need to be examined further.     

Tolerance of the newborn to antiretroviral drug exposure in utero

Introduction: The prevention of mother-to-child HIV-1 transmission by antiretroviral drug treatment is remarkably effective. The risk of transmission to the child is now almost zero for women optimally treated during pregnancy. The rapid expansion of this prophylactic treatment has led the World Health Organization to aspire to the virtual elimination of mother-to-child transmission and pediatric AIDS over the next few years. In 2014, more than 900,000 women worldwide were treated with antiretroviral drugs during pregnancy. The issue of fetal and neonatal antiretroviral drug tolerance is therefore extremely important.

Areas covered: This review focuses on the possible impact of in utero exposure to antiretroviral drug on newborn health. To restrict analysis to this period is justified by the specificities of transplacental drug exposure and fetal vulnerability. Relevant data are available from trials and observational cohorts. The significance of various bio-markers detectable at birth is still unresolved, but merits a careful evaluation. Long-term assessment is associated with various logistical difficulties.

Expert opinion: The health of ‘exposed but not infected’ children poses no major problem in the immense majority of cases, but a series of biological, clinical and imaging-based warning signs have emerged indicating the need for careful attention to be paid to this issue. Some effects that are straightforward to manage in industrialized countries may have more severe consequences in countries in which access to effective healthcare is limited. Nucleoside/nucleotide analogs are potentially genotoxic to mitochondrial and nuclear DNA, and the principal question to be addressed concerns their potential long-term effects.     

In utero preeclampsia exposure,milk intake and pubertal development

Cord blood insulin-like growth factor-1 (IGF-1) concentrations are lower in preeclamptic (PE) than normotensive (NT) pregnancies. PE offspring have increased risk of cardiovascular disease and decreased risk of some cancers including breast. We examined the effects of PE exposure in utero, infant feeding and childhood diet at 3–5 years on IGF-1 and breast development in 194 female offspring who were followed from birth until follow-ups at 10.8 and 12.9 years. Diet was not associated with serum IGF-1 levels at 10.8 years. PE exposure was associated with reduced odds of thelarche at 10.8 years only among exclusively breastfed girls. Milk, butter and ice cream consumption at 3–5 years was inversely related to the OR of breast development at 10.8 years. Child's weight and maternal overweight were positively associated with breast development at 10.8 years; child's height and weight were positively associated with breast development at 12.9 years.