Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal ...windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.
Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to ...the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation.
There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood.
A prospective, cohort study was ...conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003-2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status.
The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7-30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 95% confidence interval: 0.93-0.99). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD.
Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD.
Movements towards midline are part of the age-adequate motor repertoire of infants. They develop contemporaneously to general movements, changing from occasional simple contact to proper midline ...motor patterns.
The aim of this study is to describe the ontogeny of movements towards midline in full term healthy infants.
Parents were asked to record their infant every second week, from term age to 22 weeks post-term.
25 healthy full-term infants.
Three main epochs of development were detected: in the first one, between birth and 4 weeks post-term, movements towards midline were occasional, apparently due to the dominant flexed posture of elbow and knees and the adducted posture of shoulders and hips. In the second epoch, from 4 to 8 weeks, the limbs movements towards midline markedly decreased. In the third one, after 8 weeks, movements towards midline increased again in frequency, first appearing in lower limbs then in upper limbs, first solely as contact and thereafter as manipulation. A temporal overlapping with the occurrence of intermittent or continual fidgety movements was detected.
Movements towards midline progressively change, through a defined timeline, in full term healthy infants. The increased knowledge about the normal age-adequate motor repertoire can help physicians in clinical assessment of high risk infants.
•Movements towards midline change during time from occasional simple contacts to more advanced midline motor patterns.•Movements towards midline increase in frequency first in lower limbs and then in upper limbs.•Movements towards midline develop contemporary to fidgety movements.
Group B streptococcus (GBS) late-onset disease (LOD, occurring from 7 through 89 days of life) is an important cause of sepsis and meningitis in infants. The pathogenesis and modes of transmission of ...LOD to neonates are yet to be elucidated. Established risk factors for the incidence of LOD include maternal GBS colonisation, young maternal age, preterm birth, HIV exposure and African ethnicity. The mucosal colonisation by GBS may be acquired perinatally or in the postpartum period from maternal or other sources. Growing evidence has demonstrated the predominant role of maternal sources in the transmission of LOD. Intrapartum antibiotic prophylaxis (IAP) to prevent early-onset disease reduces neonatal GBS colonisation during delivery; however, a significant proportion of IAP-exposed neonates born to GBS-carrier mothers acquire the pathogen at mucosal sites in the first weeks of life. GBS-infected breast milk, with or without presence of mastitis, is considered a potential vehicle for transmitting GBS. Furthermore, horizontal transmission is possible from nosocomial and other community sources. Although unfrequently reported, nosocomial transmission of GBS in the neonatal intensive care unit is probably less rare than is usually believed. GBS disease can sometime recur and is usually caused by the same GBS serotype that caused the primary infection. This review aims to discuss the dynamics of transmission of GBS in the neonatal LOD.
Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome ...(ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period.
A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test.
ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.
We retrospectively investigated mother-to-infant transmission of group B Streptococcus (GBS) in 98 cases of late-onset disease reported during 2007–2018 by a network in Italy. Mothers with full ...assessment of vaginal/rectal carriage tested at prenatal screening and at time of late onset (ATLO) were included. Thirty-three mothers (33.7%) were never GBS colonized; 65 (66.3%) were vaginal/rectal colonized, of which 36 (36.7%) were persistently colonized. Mothers with vaginal/rectal colonization ATLO had high rates of GBS bacteriuria (33.9%) and positive breast milk culture (27.5%). GBS strains from mother–infant pairs were serotype III and possessed the surface protein antigen Rib. All but 1 strain belonged to clonal complex 17. GBS strains from 4 mother–infant pairs were indistinguishable through pulsed-field gel electrophoresis. At least two thirds of late-onset cases are transmitted from mothers, who often have vaginal/rectal carriage, positive breast milk culture, or GBS bacteriuria, which suggests heavy maternal colonization.
The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as “minipuberty”. There are still open questions about its biological function and significance depending on ...sex, gestational age (GA) and birth weight (BW) with few available longitudinal data.
A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile FT small for gestational age (SGA); and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points.
Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p<0.05). PT showed higher uGns levels until 3-months PTA. PT babies had higher uLH levels than FT AGA, with a peak at 7 and 30 days, during the first 90 days of life (p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs was significant (p=0.04) but not within subgroups.
This study investigated postnatal HPG axis activation in term and PT infants. Minipuberty may involve an early window of opportunity to evaluate the functionality of the HPG axis. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW.
Aim
To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic–ischemic encephalopathy (HIE).
Method
We compared ...polygraphic electroencephalography monitoring and outcome data in 39 cooled and 33 non‐cooled term newborn infants, born between January 2005 and March 2013, and hospitalized because of signs of asphyxia and moderate to severe HIE.
Results
Cooled newborn infants had fewer seizures (14/39 vs 20/33 p=0.036) and status epilepticus (7/39 vs 13/33, p=0.043), a lower mean duration of seizures (18mins vs 133mins, p=0.026), fewer administered antiepileptic drugs (median 0 vs 1, p=0.045), and more commonly a good outcome at 24 months (normal/mild motor impairment in 32/39 vs 16/33, p=0.003). Seizure burden (accumulated duration of seizures over a defined period) in cooled patients with both moderate (0.0 vs 0.1; p=0.045) and severe HIE (0.3 vs 4.9; p=0.018) was lower than in non‐cooled patients. Compared with non‐cooled patients, a good outcome was more common in cooled newborn infants with severe HIE (p=0.003).
Interpretation
Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.
What this paper adds
Cooled newborn infants with moderate and severe hypoxic–ischemic encephalopathy (HIE) have a lower seizure burden.
In cooled newborn infants with severe HIE, normal outcome at 24 months is more common.
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