Reduction In Head Circumference Research Articles

Assessment of maternal phthalate exposure in urine across three trimesters and at delivery (umbilical cord blood and placenta) and its influence on birth anthropometric measures

Phthalates, commonly used in plastic manufacturing, have been linked to adverse reproductive effects. Our research from the Saudi Early Autism and Environment Study (2019–2022), involving 671 participants, focused on the impacts of maternal phthalate exposure on birth anthropometric measures. We measured urinary phthalate metabolites in 390 maternal samples collected during each of the three trimesters of pregnancy and in cord serum and placental samples obtained at delivery. We employed various statistical methods to analyze our data. Intraclass correlation coefficients were used to assess the consistency of phthalate measurements, generalized estimating equations were used to explore temporal variations across the trimesters, and linear regression models, adjusted for significant confounders and Bonferroni correction, were used for each birth outcome. Exposure to six phthalates was consistently high across trimesters, with 82 %–100 % of samples containing significant levels of all metabolites, except for mono-benzyl phthalate. We found a 3.15 %–3.73 % reduction in birth weight (BWT), 1.39 %–1.69 % reduction in head circumference (HC), and 3.63 %–5.45 % reduction in placental weight (PWT) associated with a one-unit increase in certain urinary di(2-ethylhexyl) phthalate (DEHP) metabolites during the first trimester. In the second trimester, exposure to MEP, ∑7PAE, and ∑LMW correlated with a 3.15 %–4.5 % increase in the APGAR 5-min score and increases in PWT by 8.98 % for ∑7PAE and 9.09 % for ∑LMW. Our study also highlighted the maternal-to-fetal transfer of DEHP metabolites, indicating diverse impacts on birth outcomes and potential effects on developmental processes. Our study further confirmed the transfer of DEHP metabolites from mothers to fetuses, evidenced by variable rates in the placenta and cord serum, with an inverse relationship suggesting a passive transfer mechanism. Additionally, we observed distinct phthalate profiles across these matrices, adversely impacting birth outcomes. In serum, we noticed increases associated with DEHP metabolites, with birth gestational age rising by 1.01 % to 1.11 %, HC by 2.84 % to 3.67 %, and APGAR 5-min scores by 3.77 % to 3.87 %. Conversely, placental analysis revealed a different impact: BWT decreased by 3.54 % to 4.69 %, HC reductions ranged from 2.57 % to 4.69 %, and chest circumference decreased by 7.13 %. However, the cephalization index increased by 3.67 %–5.87 %. These results highlight the complex effects of phthalates on fetal development, indicating their potential influence on crucial developmental processes like sexual maturation and brain development.

Can ventricular 3D ultrasound of neonates with posthemorrhagic hydrocephalus inform on the need for a ventriculoperitoneal shunt?

Some neonates born prematurely with intraventricular hemorrhage develop posthemorrhagic hydrocephalus and require lifelong treatment to divert the flow of CSF. Early prediction of the eventual need for a ventriculoperitoneal shunt (VPS) is difficult, and early discussions with families are based on statistics and the grade of hemorrhage. The authors hypothesize that change in ventricular volume during ventricular taps that is measured with repeated 3D ultrasound (3D US) imaging of the lateral ventricles could be used to assess the risk of the future requirement of a VPS. A total of 92 neonates with intraventricular hemorrhage who were treated in the NICU were recruited between April 2012 and November 2019. Only patients who required ventricular taps (VTs) were included in this study, resulting in the analysis of 19 patients with a total of 61 VTs. Among them, 14 patients were treated with a VPS, and in 5 patients the hydrocephalus resolved spontaneously. Parameters studied were total ventricular volume measured with 3D US, ventricular volume change after VT, the ratio between volume reduction and tap amount, the difference between tap amount and volume reduction after tap, the average tap amount, the average number of days between taps, pre-tap head circumference, and reduction in head circumference after tap. Statistically significant differences were found in ventricular volume reduction after tap (p = 0.007), the ratio between volume reduction and tap amount (p = 0.03), the difference between tap amount and volume reduction after tap (p = 0.05), and the interval of days between taps (p = 0.0115). Measuring with 3D US before and after VT can be a useful tool for quantifying ventricular volume. The findings in this study showed that neonates who experience a large reduction of ventricular volume after VT are more likely to be treated with a shunt than are neonates who experience a small reduction.

Correlation of Facial, Dental and Oral Functions of Children with Microcephaly: Clinical Case Report

This paper discusses the orofacial manifestations of children diagnosed with severe microcephaly according to the World Health Organization. Microcephaly is a clinical condition made at or after birth that characterizes a significant reduction in head circumference, which may present craniofacial, neurological, and oral alterations as a result of this malformation. As skull growth is linked to facial growth, can patients with microcephaly have structural and functional impairments? Will these possible changes be expressed before skeletal maturity? These issues are discussed through the presentation of two relevant clinical reports of children diagnosed with severe microcephaly with similar clinical facial and occlusion patterns.. Studies along these lines should be conducted with a view to future attempts to minimize possible effects of this malformation on the craniofacial complex with preventive and interceptive therapeuticals in these individuals.

FOXG1 Gene and Its Related Phenotypes

AbstractFOXG1 is an important transcriptional repressor found in cell precursor of the ventricular region and in neurons in the early stage of differentiation during the development of the nervous epithelium in the cerebrum and optical formation. Mutations involving FOXG1 gene have been described first in subjects with congenital Rett syndrome. They can cause seizure, delayed psychomotor development, language disorders, and autism. FOXG1 deletions or intragenic mutations also determinate reduction in head circumference, structural defects in the corpus callosum, abnormal movements, especially choreiform, and intellectual retardation with no speech. Patients with duplications of 14q12 present infantile spasms and have subsequent intellectual disability with autistic features, head circumference in the normal range, and regular aspect of corpus callosum. Clinical characteristics of patients with FOXG1 variants include growth deficit after birth associated with microcephaly, facial dysmorphisms, important delay with no language, deficit in social interaction like autism, sleep disorders, stereotypes, including dyskinesia, and seizures. In these patients, it is not characteristic a history of loss of acquired skills.

Cadmium exposure and risk of adverse pregnancy and birth outcomes: a systematic review and dose-response meta-analysis of cohort and cohort-based case-control studies.

There are several inconsistencies in the epidemiological literature on the strength of the association between cadmium exposure and adverse pregnancy and birth outcomes, and the threshold dose of adverse effect. We therefore conducted a systematic review and dose-response meta-analysis to evaluate the available evidence to influence clinical decision making and better tailor public health interventions. PubMed and Scopus databases were searched up to January, 2019. Eighteen prospective studies satisfied the inclusion criteria. Random effects model was used to compute summary-effect estimates. Cadmium exposure resulted in 42.11 g (95% confidence interval [CI]: -69.03, -15.18) reduction in birth weight, and 0.105 cm (95% CI: -0.181, -0.029) reduction in head circumference per 1 µg/l increment in blood/urine cadmium levels. Cadmium exposure also resulted in 21% (RR = 1.21; 95% CI: 1.02, 1.43), 32% (RR = 1.32; 95% CI: 1.05, 1.67) and 10% (RR = 1.10; 95% CI: 0.96, 1.27) increased risk of low birth weight (LBW), preterm birth (PTB), and small-for-gestational age (SGA), respectively. Risk for all outcomes decreased with decreasing exposure. In fixed effects dose-response meta-regression analyses, we found no evidence of association of cadmium exposure with LBW and SGA. For PTB, a 1 µg/l increment in cadmium exposure corresponded to 0.5% (OR = 1.005, 95% CI: 1.003, 1.007) increase in PTB risk. Cadmium exposure was associated with risk of adverse birth outcomes. Regarding PTB, the formal dose-response meta-analyses suggests a causal association.

Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register.

BackgroundAntenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.Methods and findingsThis observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006–December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm −61.26 g (±SE 24.12, P < 0.01), preterm −232.90 g (±SE 17.24, P < .001), near term −171.50 g (±SE 17.52, P < .001), and at term −101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm −61.54 g (±SE 28.62, P < .03), preterm −222.78 g (±SE 19.64, P < .001), near term −159.25 g (±SE 19.14, P < .001), and at term −91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: −220.18 g (±SE 21.43, P < .001), −140.68 g (±SE 23.09, P < .001), and −89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.ConclusionsIn this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.

Repeat doses of antenatal betamethasone and risk factors for cardiometabolic disease at early school age.

Commentary on: McKinlay CJ, Cutfield WS, Battin MR, Dalziel SR, Crowther CA, Harding JE, ACTORDS Study Group. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT. Pediatrics 2015; 135: e405–15. McKinlay et al. 1 provides new evidence regarding some aspects of long-term safety with the use of repeated courses of antenatal corticosteroids. The original aim of the ACTORDS study was to evaluate short-term outcomes, and it has shown reduced neonatal morbidity after repeated courses of antenatal corticosteroids without an associated increase in neurologic disability at two years of corrected age or at mid-childhood 2. In the context of cardiometabolic health, the associations between preterm birth and later hypertension, diabetes, stroke and even death from cardiovascular disease 3 – boosted by animal data – have generated worries about glucocorticoid exposure in foetal life, especially if repeated. The central worry is that this glucocorticoid exposure might be in the causal pathway towards cardiometabolic disease in adult life. Previously, there had been some conflicting observational data 4-9. The long-term evaluation by McKinlay et al. carries an important message; that is, there were no adverse cardiovascular and metabolic outcomes in children exposed to repeat dose(s) of antenatal betamethasone. Although reassuring, there are some, as always, remaining questions and limitations. First, extremely preterm infants were few in the ACTORDS study. The average gestational age at study entry was >28 weeks. It cannot be excluded that extremely low gestational age at exposure may exert long-standing effects on glucose metabolism. Secondly, although six to eight years of follow-up most be considered as long term from a neonatologist's perspective, it may be too short for the outcomes addressed. Finally, the authors state that they will report other outcomes separately. These include neurologic function, lung function, general intellectual ability, specific cognitive skills, behaviour, general health and health-related quality of life. I look forward to coming reports. So what should the attending obstetrician and neonatologist recommend? The latest Cochrane review of 10 randomised trials comparing single and repeat courses of antenatal glucocorticoids for neonatal morbidity favours repeat courses. And although repeated courses have been associated with lower birthweight and small reductions in head circumference, data on long-term safety outcomes are so far generally reassuring 2. According to ACOG present guidelines, a single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than two weeks prior, the gestational age is less than 32 weeks and the women are judged by the clinician to be likely to give birth within the next week. The ACTORDS follow-up studies – the one reviewed herein and others 2 – add further support for such recommendation. https://ebneo.org/2015/05/repeat-doses-of-antenatal-betamethasone-and-risk-factors-for-cardio-metabolic-disease-at-early-school-age/ None. None.

MicroRNAs and Molecular Pathogenesis of Microcephaly.

Microcephaly is a clinical condition defined as a reduction in head circumference and brain volume. The abnormal brain size may result from pathological neural stem cell (NSC) proliferation, survival, differentiation and migration during the development of the cerebral cortex. This process is controlled by many factors, including microRNAs that normally silence target genes at the posttranscriptional level. In this review, we will discuss the roles of microRNAs involved in different stages of the cortical development to shed light on the pathogenesis of microcephaly. Understanding the molecular mechanisms of microRNA-mediated cortical development may help develop a means of microRNA-based diagnosis and treatment for microcephaly in humans.

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Cadmium May Affect Newborn Girls More than Boys: Maternal Exposure Linked to Smaller Birth Size

Vol. 120, No. 2 News | Science SelectionsOpen AccessCadmium May Affect Newborn Girls More than Boys: Maternal Exposure Linked to Smaller Birth Sizeis accompanied byMaternal Cadmium Exposure during Pregnancy and Size at Birth: A Prospective Cohort Study Julia R. Barrett Julia R. Barrett Search for more papers by this author Published:1 February 2012https://doi.org/10.1289/ehp.120-a76bCited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Chronic exposure to cadmium, which primarily occurs through diet and smoking, damages the kidneys, weakens bones, and may increase cancer risk. The metal is also an endocrine disrupter and may adversely affect reproduction and child development. Animal studies indicate cadmium induces multiple defects in developing embryos, but it is unknown whether similar effects occur in humans. However, a new study shows that maternal cadmium exposure is associated with reduced head circumference and birth weight in newborn girls [EHP 120(2):284–289; Kippler et al.].The study used data collected from more than 1,600 pregnant women participating in the Maternal and Infant Nutrition Interventions, a food and micronutrient supplementation trial in Matlab, Bangladesh. The women provided urine samples and completed clinical examinations in early pregnancy. Information on demographics and tobacco and betel use during pregnancy also was collected, along with newborns’ sex and physical measurements.Average adult daily intakes of cadmium were estimated on the basis of rice consumption to be 25–35 µg, similar to those in other Asian countries where rice is a staple but higher than levels reported in U.S. and European women. Statistical analyses, controlled for confounding by maternal, birth, and newborn factors, suggested that for each 1-µg/L increase in maternal urinary cadmium, head circumference decreased by 0.26 cm and weight dropped by 45 g on average among newborn girls. Far smaller associations were seen for boys.Cadmium may affect fetal growth by several mechanisms, including impaired nutrient transport and endocrine disruption. Sex-based differences in specific hormone levels as well as in cadmium uptake and mechanisms of action—which have been reported in experimental studies—may have played a role in the current findings. The authors say the estimated average reductions in head circumference and weight are unlikely to be clinically significant for individual children but could have public health implications given widespread dietary cadmium exposure and adverse effects associated with reduced birth size.The main strengths of the study are its prospective design, large number of participants, wide range of exposure, and consideration of numerous confounding factors. However, the potential for unmeasured or residual confounding remained, as in all observational studies, and infants’ cadmium exposure was not directly assessed (for instance, by measuring cadmium levels in cord blood). Continuing research should follow the children to determine if growth effects are sustained through childhood and whether other health changes appear later in childhood.Asian diets high in rice consumption may lead to elevated cadmium intake, which has been linked to reduced birth size in girls.© 2012 G.M.B. Akash/Panos PicturesFiguresReferencesRelatedDetailsCited by Real M, Azam H and Majed N (2017) Consumption of heavy metal contaminated foods and associated risks in Bangladesh, Environmental Monitoring and Assessment, 10.1007/s10661-017-6362-z, 189:12, Online publication date: 1-Dec-2017. Tang M, Xu C, Lin N, Liu K, Zhang Y, Yu X and Liu W (2016) Lead, mercury, and cadmium in umbilical cord serum and birth outcomes in Chinese fish consumers, Chemosphere, 10.1016/j.chemosphere.2016.01.058, 148, (270-275), Online publication date: 1-Apr-2016. Related articlesMaternal Cadmium Exposure during Pregnancy and Size at Birth: A Prospective Cohort Study23 August 2011Environmental Health Perspectives Vol. 120, No. 2 February 2012Metrics About Article Metrics Publication History Originally published1 February 2012Published in print1 February 2012 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.

Giant syringobulbia associated with cerebellopontine angle arachnoid cyst and hydrocephalus

The aim in reporting this case was to discuss the pathophysiology and treatment issues in an infant with a giant syringobulbia associated with a right cerebellopontine angle (CPA) arachnoid cyst causing noncommunicating hydrocephalus. This 7-month-old infant presented to the hospital with a history of delayed milestones and an abnormal increase in head circumference. Magnetic resonance images and CT scans of the brain showed a large CSF cavity involving the entire brainstem and a right CPA arachnoid cyst causing obstruction of the fourth ventricle and dilation of the lateral and third ventricles. Cerebrospinal fluid diversion was performed by direct communication from the syringobulbia cavity to the left lateral ventricle and from the left lateral ventricle through another ventricular catheter; external ventricular drainage was performed temporarily for 5 days. Communication between the syrinx and arachnoid cyst was confirmed. Clinically, there was a reduction in head circumference, and serial MR imaging of the brain showed a decrease in the size of the syrinx cavity and the ventricle along with opening of the normal CSF pathways. The postoperative course was uneventful, and no further intervention was necessary. On follow-up of the child at 3 years, his developmental milestones were normal. Surgical intervention for this condition is mandatory. The appropriate type of surgery should be performed on the basis of the pathophysiology of the developing syringobulbia.

Early postnatal blood concentrations of inflammation-related proteins and microcephaly two years later in infants born before the 28th post-menstrual week

Background To evaluate if concentrations of inflammation-related proteins were elevated in early postnatal blood specimens of preterm newborns who two years later had a small head. Methods We measured 25 proteins in blood collected on days 1, 7, and 14 from 839 infants born before the 28th week of gestation and whose head circumference was measured at birth and near 24-months post-term equivalent. We excluded children whose birth head circumference was at or below the third centile. A protein concentration was considered elevated if it was in the highest quartile for gestational age and the day the specimen was obtained. Findings When proteins were evaluated individually, elevated concentrations of SAA on day 1 and five proteins on day 14, IL-6, TNF-R2, IL-8, MCP-1, and ICAM-1 were associated with significantly increased risk of microcephaly (head circumference Z-score <−2). The ten proteins whose elevated concentrations on two separate days a week apart predicted microcephaly, but did not do so when elevated on only one of these days were CRP, SAA, IL-1β, IL-6, TNF-α, IL-8, MCP-1, ICAM-1, E-SEL, IGFBP-1. Elevated protein concentrations weakly predicted a less severe reduction in head circumference (Z-score ≥ − 2, < − 1). Interpretation Concentrations of inflammation-related proteins in the circulation shortly after preterm birth provide information about the risk of a reduced head circumference more than two years later. Funding The ELGAN Study was supported by a cooperative agreement with the National Institute of Neurological Disorders and Stroke of the United States.

Does in utero exposure to synthetic glucocorticoids influence birthweight, head circumference and birth length? A systematic review of current evidence in humans

Synthetic glucocorticoids are the mainstay treatment for stimulating lung maturation in threatened preterm delivery. Animal studies suggest that in utero exposure to glucocorticoids leads to a reduction in birth size. Smaller birthweight has been associated with higher risk of many chronic diseases. Therefore, the authors undertook a systematic review of human studies examining the association between synthetic glucocorticoid treatment and birth size. Medline, EMBASE, PubMed, Cochrane, Google scholar and Institute of Life Science databases were searched for studies published between 1978 and 2009 investigating the association between synthetic glucocorticoids and birthweight, head circumference, birth length and ponderal index. All studies controlling for gestational age were examined. Seventeen studies were included in the analysis. Nine out of 17 studies reported a reduction in birthweight (range 12-332 g), five of nine a reduction of head circumference (range 0.31-1.02 cm) and two of four a reduction of 0.8 cm in birth length. Despite methodological inconsistencies and limitations that impede clear conclusions, the evidence suggests an association between in utero exposure to synthetic glucocorticoids and reduced birth size.

Antenatal antecedents of a small head circumference at age 24-months post-term equivalent in a sample of infants born before the 28th post-menstrual week

Background Little is known about the antecedents of microcephaly in early childhood among children born at extremely low gestational age. Aim To identify some of the antecedents of microcephaly at age two years among children born before the 28th week of gestation. Study design Observational cohort study. Subjects 1004 infants born before the 28th week of gestation. Outcome measures Head circumference Z-scores of <−2 and ≥−2, <−1. Results Risk of microcephaly and a less severely restricted head circumference decreased monotonically with increasing gestational age. After adjusting for gestational age and other potential confounders, the risk of microcephaly at age 2 years was increased if microcephaly was present at birth [odds ratio: 8.8 ((95% confidence interval: 3.7, 21)], alpha hemolytic Streptococci were recovered from the placenta parenchyma [2.9 (1.2, 6.9)], the child was a boy [2.8 (1.6, 4.9)], and the child's mother was not married [2.5 (1.5, 4.3)]. Antecedents associated not with microcephaly, but with a less extreme reduction in head circumference were recovery of Propionibacterium sp from the placenta parenchyma [2.9 (1.5, 5.5)], tobacco exposure [2.0 (1.4, 3.0)], and increased syncytial knots in the placenta [2.0 (1.2, 3.2)]. Conclusions Although microcephaly at birth predicts a small head circumference at 2 years among children born much before term, pregnancy and maternal characteristics provide supplemental information about the risk of a small head circumference years later. Two findings appear to be novel. Tobacco exposure during pregnancy, and organisms recovered from the placenta predict reduced head circumference at age two years.

366 Chemotherapy-induced venous thromboembolism is not due to endothelial cell activation

To evaluate if concentrations of inflammation-related proteins were elevated in early postnatal blood specimens of preterm newborns who two years later had a small head.We measured 25 proteins in blood collected on days 1, 7, and 14 from 839 infants born before the 28th week of gestation and whose head circumference was measured at birth and near 24-months post-term equivalent. We excluded children whose birth head circumference was at or below the third centile. A protein concentration was considered elevated if it was in the highest quartile for gestational age and the day the specimen was obtained.When proteins were evaluated individually, elevated concentrations of SAA on day 1 and five proteins on day 14, IL-6, TNF-R2, IL-8, MCP-1, and ICAM-1 were associated with significantly increased risk of microcephaly (head circumference Z-score <−2). The ten proteins whose elevated concentrations on two separate days a week apart predicted microcephaly, but did not do so when elevated on only one of these days were CRP, SAA, IL-1β, IL-6, TNF-α, IL-8, MCP-1, ICAM-1, E-SEL, IGFBP-1. Elevated protein concentrations weakly predicted a less severe reduction in head circumference (Z-score ≥ − 2, < − 1).Concentrations of inflammation-related proteins in the circulation shortly after preterm birth provide information about the risk of a reduced head circumference more than two years later.The ELGAN Study was supported by a cooperative agreement with the National Institute of Neurological Disorders and Stroke of the United States.

Smoking and smoking cessation during early pregnancy and its effect on adverse pregnancy outcomes and fetal growth

Maternal smoking during pregnancy is a significant threat to the fetus. We examined the association between active maternal smoking and smoking cessation during early pregnancy with newborn somatometrics and adverse pregnancy outcomes including preterm delivery, low birth weight, and fetal growth restriction. One thousand four hundred mother-child pairs with extensive questionnaire data were followed up until delivery, within the context of a population-based mother-child cohort study (Rhea study), in Crete, Greece, 2007-2008. Comparing smokers to nonsmokers, the adjusted odds ratio (OR) was 2.8 [95% confidence interval (CI), 1.7, 4.6] for low birth weight and 2.6 (95%CI: 1.6, 4.2) for fetal growth restriction. This corresponded to a 119-g reduction in birth weight, a 0.53-cm reduction in length, and a 0.35-cm reduction in head circumference. Smoking cessation early during pregnancy modified significantly these pregnancy outcomes indicating the necessity for primary smoking prevention.

The Effect of Ambient Air Pollution during Early Pregnancy on Fetal Ultrasonic Measurements during Mid-Pregnancy

BackgroundOver the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth.ObjectivesThis study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13–26 weeks gestation) and ambient air pollution during early pregnancy.MethodsWe calculated mothers’ average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter < 10 μm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother’s age, socioeconomic status, and fetal sex.ResultsA reduction in fetal AC was associated with O3 during days 31–60 [−1.42 mm; 95% confidence interval (CI), −2.74 to −0.09], SO2 during days 61–90 (−1.67 mm; 95% CI, −2.94 to −0.40), and PM10 during days 91–120 (−0.78 mm; 95% CI, −1.49 to −0.08). Other results showed a reduction in BPD (−0.68 mm; 95% CI, −1.09 to −0.27) associated with SO2 during days 0–30, a reduction in HC (−1.02 mm; 95% CI, −1.78 to −0.26) associated with PM10 during days 91–120, and a reduction in FL associated with PM10 during days 0–30 (−0.28 mm; 95% CI, −0.48 to −0.08) and 91–120 (−0.23; 95% CI, −0.42 to −0.04).ConclusionWe found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results.

Low levels of ambient air pollution during pregnancy and fetal growth among term neonates in Brisbane, Australia

There is mounting evidence that maternal exposure to ambient air pollution during pregnancy is associated with adverse birth outcomes. We examined birth weight and small for gestational age (SGA <10th percentile for age and gender) among 26,617 singleton full-term births in Brisbane, Australia (July 2000–June 2003), in relation to ambient pollution during pregnancy. We also examined head circumference (HC) and crown–heel length (CHL) among a sub-sample ( n=21,432) of the term neonates. Maternal exposure to PM 10, visibility reducing particles (bsp), O 3 and NO 2 was assessed by calculating average exposure estimates over months and trimesters of pregnancy based on a citywide average of the pollutants. Linear and logistic regression models were employed to examine the effect of these pollutants on the birth outcomes after adjusting for potential confounders and season of birth. The regression coefficients were based on an inter-quartile range (IQR) increase in exposure as well as quartiles of exposure with the lowest used as a reference category. Trimester- and monthly specific exposures to all pollutants were not significantly associated with a reduction in either birth weight or HC, or an increased risk of SGA. An IQR increase in NO 2 during the third trimester was associated with a reduction in CHL ( β = - 0.15 cm, 95% CI −0.25 to −0.05 cm) and this was concentrated around exposure during month nine. No other pollutants were associated with a reduction in CHL. In conclusion, there was no strong evidence suggesting that ambient air pollution during pregnancy is associated with sub-optimal fetal growth in Brisbane.