Asymptomatic bacteriuria (ASB) is a well-acknowledged infectious entity during pregnancy; yet its long-term implications are not well investigated. The present study aimed to test the association between maternal ASB during pregnancy and long-term offspring infectious hospitalizations. A population-based cohort analysis was conducted, comparing the incidence of long-term infectious-related hospitalizations of offspring born to mothers who were diagnosed with ASB during pregnancy, and those who did not have ASB. The study was conducted at a tertiary medical center and included all singleton deliveries between the years 1991 and 2014. Infectious morbidities were based on a predefined set of International Classification of Disease-9 codes. A Kaplan−Meier survival curve compared cumulative infectious hospitalization incidence between the groups, and a Cox regression model was used to adjust for confounding variables. During the study period, 212,984 deliveries met inclusion criteria. Of them, 5378 (2.5%) were diagnosed with ASB. As compared to offspring of non-ASB mothers, total long-term infectious hospitalizations were significantly higher among children to mothers who were diagnosed with ASB (13.1% vs. 11.1%, OR = 1.2, 95% CI 1.11–1.30, P ≤ 0.001). Likewise, a Kaplan−Meier curve demonstrated higher cumulative incidence of infectious hospitalizations among children born to mothers with ASB (log rank, P = 0.006). In the Cox regression model, while controlling for maternal age, diabetes mellitus, ethnicity, hypertensive disorders, and gestational age, maternal ASB was noted as an independent risk factor for long-term infectious morbidity in the offspring (adjusted HR = 1.1, 95% CI 1.01–1.17, P = 0.042). ASB during pregnancy increases offspring susceptibility to long-term infectious hospitalizations.

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal–fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life.

There is mounting evidence to implicate the intrauterine environment as the initial pathogenic stage for neuropsychiatric disease. Recent developments in magnetic resonance imaging technology are making a multimodal analysis of the fetal central nervous system a reality, allowing analysis of structural and functional parameters. Exposures to a range of pertinent risk factors whether preconception or in utero can now be indexed using imaging techniques within the fetus’ physiological environment. This approach may determine the first “hit” required for diseases that do not become clinically manifest until adulthood, and which only have subtle clinical markers during childhood and adolescence. A robust characterization of a “multi-hit” hypothesis may necessitate a longitudinal birth cohort; within this investigative paradigm, the full range of genetic and environmental risk factors can be assessed for their impact on the early developing brain. This will lay the foundation for the identification of novel biomarkers and the ability to devise methods for early risk stratification and disease prevention. However, these early markers must be followed over time: first, to account for neural plasticity, and second, to assess the effects of postnatal exposures that continue to drive the individual toward disease. We explore these issues using the schizophrenia spectrum disorders as an illustrative paradigm. However, given the potential richness of fetal magnetic resonance imaging, and the likely overlap of biomarkers, these concepts may extend to a range of neuropsychiatric conditions.

There is an established link between birth parameters and risk of adult-onset cancers. The Developmental Origins of Health and Disease concept provides potential underlying mechanisms for such associations, including intrauterine exposure to endogenous hormones (androgens and estrogens), insulin-like growth factors, etc. However, there is conflicting evidence on the association between birth parameters and the cancer mortality risk. Therefore, we aimed to review and analyse the available data on the association linking birth weight and birth length with cancer mortality. Eleven studies were identified, published until April 2019. A significant association between birth weight and the prognosis of cancer (overall) was found (relative risk, RR 1.06, 95% confidence interval, CI: 1.01, 1.11), with low heterogeneity (I2 = 27.7%). In addition, higher birth weight was associated with poorer prognosis of prostate cancer (RR 1.21, 95% CI: 1.02, 1.44). However, the association of birth weight with breast cancer mortality risk in women was not significant (RR 1.16, 95% CI: 0.93, 1.44), which might be due to high statistical heterogeneity (I2 = 67.9%). Birth length was not associated with cancer mortality risk (RR 1.0, 95% CI: 0.90–1.11). It might be inferred that birth parameters are not associated with cancer mortality as strongly as with the risk of developing cancer. Also, the association between birth parameters and cancer mortality risk is not uniform and varies according to its subtypes, and study characteristics/design. This highlights the need for further prospective studies.

Fetal hydrops is a serious complication of immune-mediated congenital complete atrioventricular block. We present the case of a fetus with severe hydrops and profound bradycardia and an unusual favourable outcome. This case enhances the importance of considering the contribution of ventricular ectopic beats to the cardiac output when counselling and predicting outcome of complete heart block.

Objectives were to determine the effects of advancing gestation, maternal nutrient restriction during early and mid-gestation, and realimentation on fetal liver and jejunal mass and energy use in both dams and fetuses. On day 30 of pregnancy, multiparous, non-lactating beef cows (initial BW=621±11.3 kg and body condition score=5.1±0.1) were assigned to one of the two dietary treatments: control (CON; 100% requirements; n=18) and restricted (R; 60% requirements; n=28). On day 85, cows were slaughtered (CON, n=6; R, n=6), and remaining cows continued on control (CC; n=12) and restricted (RR; n=12) diets, or were realimented to the control diet (RC; n=11). On day 140, cows were slaughtered (CC, n=6; RR, n=6; RC, n=5), remaining cows continued on the control diet (CCC, n=6; RCC, n=5), or were realimented to the control diet (RRC, n=6). On day 254, all remaining cows were slaughtered. Maternal liver O2 consumption linearly increased (P⩽0.04) and jejunal weight (g/kg) linearly decreased (P=0.04) as gestation advanced in CON groups. Fetal BW, and hepatic and small intestinal absolute mass, protein content and O2 consumption linearly increased (P⩽0.04) as pregnancy advanced in CON groups. However, mass and O2 consumption relative to BW linearly decreased (P⩽0.001) in the fetal liver in CON groups. When analyzing the effects of dietary treatment, at day 85, fetal jejunal O2 consumption (mol/min per kg BW) was lower (P=0.02) in the R group when compared with the CON group. At day 140, maternal hepatic weight (g) was lower (P=0.02) in RC and RR cows when compared with CC, and fetal jejunual O2 consumption (mmol/min per mg tissue and mmol/min per g protein) was greater (P⩽0.02) in RC when compared with RR. At day 254, maternal hepatic O2 consumption (absolute and relative to BW) was lower (P⩽0.04) in the RCC cows when compared with RRC. Fetal hepatic weight was lower (P=0.05) in the CCC group when compared with RCC and RRC. The changes in response to nutrient restriction and realimentation in both the dam and fetus may indicate an adaptation to a lower amount of available nutrients by altering tissue mass and metabolism.

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov–Smirnov test, P-value<10–15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (rS-values>−0.62), but in girls only 207 (41%) showed inverse correlation (rS-values>−0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.

Theories regarding the relationship between pre- and postnatal growth and programming of health have been based on characteristics at birth, with little or no reference to the patterns of growth occurring in utero. Review of the literature to identify studies using ultrasonographically obtained fetal dimensions to track prenatal growth and relate these patterns of growth to postnatal anthropometry and cardiovascular and metabolic risk factors. Review of Medline, Scopus and Proquest for studies reporting on ultrasonographically derived estimates of fetal growth and their association with postnatal anthropometry, body composition or cardiovascular and metabolic risk factors. Quality of papers were assessed using the method developed by Downs and Black. Twenty-nine studies met the inclusion criteria, with a mean score of high quality. Twenty of the studies had follow-up in infancy, five in childhood, three in adolescence and one in adulthood. The associations observed suggest that centile tracking may occur early in pregnancy though whether this is as early as the first trimester is uncertain. The second trimester may be a critical period for the programming of blood pressure and abdominal circumference may be the most sensitive fetal dimension to indicate any programming.

The analysis of genetic and environmental contributions to preterm birth is not straightforward in family studies, as etiology could involve both maternal and fetal genes. Markov Chain Monte Carlo (MCMC) methods are presented as a flexible approach for defining user-specified covariance structures to handle multiple random effects and hierarchical dependencies inherent in children of twin (COT) studies of pregnancy outcomes. The proposed method is easily modified to allow for the study of gestational age as a continuous trait and as a binary outcome reflecting the presence or absence of preterm birth. Estimation of fetal and maternal genetic factors and the effect of the environment are demonstrated using MCMC methods implemented in WinBUGS and maximum likelihood methods in a Virginia COT sample comprising 7,061 births. In summary, although the contribution of maternal and fetal genetic factors was supported using both outcomes, additional births and/or extended relationships are required to precisely estimate both genetic effects simultaneously. We anticipate the flexibility of MCMC methods to handle increasingly complex models to be of particular relevance for the study of birth outcomes.

The fetal insulin hypothesis proposes that low birth weight and susceptibility to type 2 diabetes (T2D) could both be two phenotypes of the same genotype. Insulin is a key growth factor in utero, and T2D is characterized by insulin resistance and/or beta-cell dysfunction. Therefore, genetic variants impacting on insulin secretion and action are likely to alter both fetal growth and susceptibility to T2D. There are three lines of evidence in support of this hypothesis. (1) Studies of rare monogenic diabetes have shown mutations in a single gene, such as GCK or KCNJ11, can cause diabetes by reducing insulin secretion, and these mutations are also associated with reduced birth weight. (2) Epidemiological studies have indicated that children born to fathers with diabetes are born smaller. As the father cannot influence the intrauterine environment, this association is likely to reflect genes inherited by the fetus from the father. (3) The most compelling evidence comes from recent genome-wide association studies. Variants in the CDKAL1 and HHEX-IDE genes that predispose to diabetes, if present in the fetus, are associated with reduced birth weight. These data provide evidence for a genetic contribution to the association between low birth weight and susceptibility to T2D. This genetic background is important to take into consideration when investigating the impact of environmental determinants and developing strategies for intervention and prevention.

Between 1989 and 2000, 21 fetuses were diagnosed with complete atrioventricular block. Seven women with fetal ventricular rates of less than 60 were given oral terbutaline, and 6 of these had an initial increase in the fetal ventricular rate. Four fetuses (57%) maintained an increased average rate of 60 beats per minute and survived. Two fetuses returned to rates below 55 and died. The final fetus, with hypertrophic cardiomyopathy, was unresponsive. Terbutaline, therefore, is initially effective in raising the fetal ventricular rate, but this effect may be transient.

Introduction: The frequent occurrence of prenatal hypertrophy of the muscular ventricular septum has been widely reported in fetuses of diabetic mothers. Objectives: This experimental study was carried out to test the hypothesis that the weight of the heart, the ratio of the cardiac weight to that of the body, the thickness of the muscular ventricular septum, and the myocytic profile within the ventricular septum are all increased in fetuses of diabetic rats in comparison to fetuses of normal rats. Methods: Diabetes was induced in 5 pregnant Wistar rats, bearing 30 fetuses, on the eighth day after conception, by intraperitoneal injection of 50mg/kg of streptozotocin. Five normal pregnant Wistar rats, bearing 20 fetuses, made up the control group. Morphometric data were obtained by a computer-assisted method applied to the measurements of the thickness of the ventricular septum, and myocytic nuclear area. Statistical analysis utilized Student's t-test and Kruskal-Wallis test. Results: The mean thickness of the septum was 675.56 μm (± 159) in the control fetuses, and 904.39 μm (± 262) in the fetuses carried by diabetic mothers (p < 0.001). The cardiac weight was 0.016 g (± 0.004) in the control group, and 0.023 g (± 0.005) in the group of diabetic fetuses (p < 0.001). The ratio of cardiac to body weight was 0.294% (± 0.079) in the control group, and 0.514% (± 0.073) in the diabetic group (p < 0.001). The myocytic nuclear area was 14.70 μm2 in the control group, and 21.43 μm2 in the diabetic group (p < 0.001). Conclusions: The presence of cellular and morphologic cardiac hypertrophy in fetuses of diabetic rats was demonstrated by the significant difference between the two groups for each analyzed feature.

Each somatic cell of the human body contains 46 chromosomes consisting of two sets of 23; one inherited from each parent. These chromosomes can be categorised as 22 pairs of autosomes and two sex chromosomes; females are XX and males are XY. Similarly, at the molecular level, two copies of each autosomal gene exist; one copy derived from each parent. Until the mid-1980s, it was assumed that each copy of an autosome or gene was functionally equivalent, irrespective of which parent it was derived from. However, it is now clear from classical experiments in mice and from examples of human genetic disease that this is not the case. The functional activity of some genes or chromosomal regions is unequal, and dependent on whether they have been inherited maternally or paternally. This phenomenon is termed ‘genomic imprinting’ and the activity or silence of an imprinted gene or chromosomal region is set during gametogenesis. Genomic imprinting involving the autosomes appears to be restricted to eutherian mammals, and has most likely evolved as a result of the conflicting concerns of the parental genomes in the growth and development of their offspring. When the normal pattern of imprinting is disrupted, the phenotypes observed in humans and mice are generally associated with abnormal fetal growth, development and behaviour, illustrating its importance for a normal intrauterine environment. The characteristics of imprinted genes, their regulation and the phenotypes associated with altered imprinting are discussed.