The perinatal period is crucial to the establishment of lifelong gut microbiota. The abundance and composition of microbiota can be altered by several factors such as preterm delivery, formula feeding, infections, antibiotic treatment, and lifestyle during pregnancy. Gut dysbiosis affects the development of innate and adaptive immune responses and resistance to pathogens, promoting atopic diseases, food sensitization, and infections such as necrotizing enterocolitis (NEC). Recent studies have indicated that the gut microbiota imbalance can be restored after a single or multi-strain probiotic supplementation, especially mixtures of Lactobacillus and Bifidobacterium strains. Following the systematic search methodology, the current review addresses the importance of probiotics as a preventive or therapeutic tool for dysbiosis produced during the perinatal and infant period. We also discuss the safety of the use of probiotics in pregnant women, preterm neonates, or infants for the treatment of atopic diseases and infections.

Maternal tobacco smoking during pregnancy remains a major public health issue. The neurotoxic properties of nicotine are associated with fetal neurodevelopmental disorders and perinatal morbimortality. Recent research has demonstrated the effects of nicotine toxicity on genetic and epigenetic alterations. Smoking cessation strategies including nicotine replacement therapy (NRT) and electronic nicotine delivery systems (ENDS) show lack of clear evidence of effectiveness and safety in pregnant women. Limited trials using randomized controls concluded that the intermittent use formulation of NRT (gum, sprays, inhaler) in pregnant women is safe because the total dose of nicotine delivered to the fetus is less than continuous-use formulations (transdermal patch). Electronic nicotine delivery systems (ENDS) were hyped as a safer alternative during pregnancy. However, refill liquids of ENDS are suspected to be cytotoxic for the fetus. Animal studies revealed the impact of ENDS on neural stem cells, showing a similar risk of pre- and postnatal neurobiological and neurobehavioral disorders to that associated with the exposure to traditional tobacco smoking during early life. There is currently no clear evidence of impact on fetal brain development, but recent research suggests that the current guidelines should be reconsidered. The safety of NRT and ENDS is increasingly being called into question. In this review, we discuss the special features (pharmacodynamics, pharmacokinetics, and metabolism) of nicotine, NRT, and ENDS during pregnancy and postnatal environmental exposure. Further, we assess their impact on pre- and postnatal neurodevelopment.

Listeria monocytogenes (Lm) is a gram-positive bacillus which causes neonatal listeriosis (NL). NL is caused by vertical transmission (transplacental, ascending or birth canal related) or less frequently by nosocomial infection. In healthy people, Lm infections may be asymptomatic or cause unspecific flu-like or gastrointestinal symptoms. However, in immunocompromised patients including elderly people, pregnant women or neonates, Lm may cause fatal infections. Mortality can be high (up to 45%), as can be the rate of neurologic complications (Siegman-Igra Y et al., Emerg. Infect. Dis. 2002; 8: 305–310). In 2014, the European Centre for Disease Prevention and Control (ECDC) reported 2.194 listeriosis cases (case rate 0.6/100.000 population) with highest rates in infants below one year of age (case rate 2.8/100.000 population) observing rising tendency. In that year, 161 of the cases (all age groups) were declared in Spain (case rate 1.2/100.000 population) (Annual Epidemiological Report - Listeria, ECDC 2016). On the other hand, spontaneous abortions and stillbirths wrongly not related with Lm may underestimate real prevalence. In neonates, Lm can cause 2 different patterns of disease. First, an early-onset disease due to vertical infection (serotypes 1a, 1b 4b) associated with premature birth, meconium staining of amniotic fluid (MSAF) and sepsis. Second, a late-onset disease due to vertical or nosocomial infection (serotypes 4b) and most common in term babies causing meningitis. Microbiological detection can be challenging as the poor specificity of blood cultures and Cerebral Spinal Fluid (CSF) cultures. Clinical guidelines for neonatal early-onset sepsis (EOS) evaluation do not recommend or pay little attention to body surface cultures (BSC) (Centers for Disease Control and Prevention. MMWR 2010; 59: 1–23), (Polin R et al., Pediatrics 2012; 129: 1006–1015). In cases of suspected EOS we perform BSC routinely in our neonatal tertiary care unit. In this report we evaluate NL biological testing with focus on BSC.

Pallister-Killian syndrome (PKS; OMIM 601803) was first described in 1977 by the American physician Philip Pallister and later in 1981 by the Austrian physician Wolfgang Killian. PKS is a rare chromosomal disorder due to a sporadic mosaic tetrasomy of the short arm of isochromosome 12 (i12p). Hexasomic forms (2 isochromosomes) or the presence of a ring chromosome have been described. Prenatal ultrasound may show polyhydramnios, rhizomelic micromelia or macrosomia (Lloveras E et al., Fetal Diagn Ther 2013; 34: 172–175). Main clinical features in the newborn are hypotonia, feeding difficulties, pigmentary skin anomalies and seizures but physical head exam may give the clue for diagnosis. Hypertelorism, small nose, long philtrum, V-shaped upper lip (“Pallister lip”), low set posteriorly rotated ears, bilateral frontotemporal alopecia and a coarse facies (more pronounced with age) are characteristic for PKS. Further congenital cardiac defects, diaphragmatic hernia, renal or anal malformations may be associated. A phenotypical study of 22 PKS patients showed that profound intellectual disability is not universal, a considerable percentage of patients presented mild or moderate disability (Blyth M et al., J Med Genet 2015; 52: 454–464). Increased maternal age is an independent risk factor for PKS. i12p can be detected prenatally in chorionic villus and amniotic fluid cell samples or later in lymphocytes and skin fibroblast cultures. No evidence of genotype-phenotype correlation was found in PKS (Doray B et al., Prenat Diagn 2002; 22: 470–477). We describe a clinical case of PKS in a late premature patient without prenatal diagnosis. The mother has given written consent for the publication.