[Two Cases of Pseudo-Bartter Syndrome in Childhood: When to Suspect a Rare Onset Pattern of Cystic Fibrosis].

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer. In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one.

Spontaneous hemoperitoneum in pregnancy: Italian prospective population-based cohort study.

INTRODUCTION: Spontaneous hemoperitoneum in pregnancy is defined as a sudden non-traumatic intraperitoneal bleeding in pregnancy and up to 42 days postpartum. In the present study we aim to estimate the incidence and investigate the risk factors, the management and the outcomes of spontaneous hemoperitoneum in pregnancy in order to improve its clinical identification and reduce avoidable maternal deaths. MATERIAL AND METHODS: This is a prospective population-based cohort study, set in maternity units from nine Italian regions covering 75% of the national births. The study population comprises all women admitted for spontaneous intraperitoneal hemorrhage during pregnancy and up to 42 days postpartum between November 2017 and March 2020. Incident cases were reported by trained clinicians through electronic data collection forms. Descriptive statistics were performed. The main outcome measures included incidence rate of spontaneous hemoperitoneum in pregnancy, association with potential risk factors, clinical management and maternal and perinatal outcomes. RESULTS: Twenty-nine cases met the adopted definition of spontaneous hemoperitoneum in pregnancy with an estimated incidence rate of 0.04 per 1000 births. An increased risk ratio (RR) of this condition was observed in pregnancies conceived by assisted reproductive technology (RR = 6.60, 95% CI 2.52-17.29), in the case of multiple pregnancies (RR = 6.57, 95% CI 1.99-21.69) and maternal age ≥35 years (RR 2.10, 95% CI 1.01-4.35). In 17/29 cases the bleeding site was intra-pelvic (23.5% in the posterior uterine wall and 35.2% in the left hemipelvis). Laparotomy represented the surgical treatment in 27 cases (93%), and most women underwent a cesarean delivery (92.6%). Median blood loss was 1900 mL, one hysterectomy was necessary, and two women died. Twenty-two preterm births were recorded. CONCLUSIONS: Spontaneous hemoperitoneum in pregnancy is a rare, life-threatening condition associated with high perinatal morbidity and mortality. Maternal age ≥35 years, multiple pregnancies and assisted reproductive technology were associated to a higher risk of the condition. Two women of 29 died and 70% of births occurred preterm.

Management of Breast Abscess during Breastfeeding.

(1) Background: Breast abscess (BA) is a condition leading in the majority of cases to breastfeeding interruption. Abscesses are commonly treated with antibiotics, needle aspiration or incision and drainage (I&D), but there is still no consensus on the optimal treatment. Since there are no well-defined clinical guidelines for abscess management, we conducted a retrospective, observational study with the aim of assessing ultrasound (US)-guided management of BA without surgery, regardless of the BA size. The secondary objective was the microbiologic characterization and, in particular, the S. aureus methicillin resistance identification. (2) Methods: our population included 64 breastfeeding mothers with diagnosis of BA. For every patient, data about maternal, perinatal and breastfeeding features were collected. All patients underwent office US scans and 40 out of 64 required a more detailed breast diagnostic ultrasound performed by a radiologist. In all cases, samples of milk or abscess material were microbiologically tested. All patients received oral antibiotic treatment. We performed needle aspiration, when feasible, even on abscesses greater than 5 cm. (3) Results: most of the women developed BA during the first 100 days (68.8% during the first 60 days) after delivery and 13 needed hospitalization. Four abscesses were bilateral and 16 had a US major diameter greater than 5 cm. All patients were treated with antibiotic therapy according to our clinical protocol and 71.9% (46/64) underwent fine needle aspiration. None of them required I&D. The average duration of breastfeeding was 5 months (IR 2; 9.5) and 40.6% of women with BA continued to breastfeed for more than 6 months. Only 21 mothers interrupted breastfeeding before 3 months. (4) Conclusions: our observational data suggest, regardless of the size and the clinical features of the BA, a conservative approach with antibiotic therapy targeted at the Methicillin-Resistant Staphilococcus aureus (MRSA) identified and needle aspiration, if feasible. In our experience, treatment with needle aspiration is a cost- effective method. Unlike drainage, it is an outpatient procedure, easily repeatable, with no cosmetic damage. In addition, it has lower risk of recurrences since, differently from surgical incision, it does not cause interruption of the ducts. Moreover, needle aspiration is less painful, does not require the separation of the mother-child dyad and allows for a quicker, if not immediate, return to breastfeeding.

Breastfeeding: Biological and Social Variables in Different Modes of Conception.

BACKGROUND: Breastfeeding has effects on health throughout the lives of mothers and babies. In 2014 in Italy, 10,976 babies were born through ART (assisted reproductive technology), accounting for 2.2% of annual births. The study aims to assess how both social and biological variables and the mode of conception influence breastfeeding. METHODS: This observational study involves 161 pregnancies from three different modes of conception: homologous in vitro fertilization, ovum donation, and spontaneous pregnancies. Neonatal and maternal characteristics were collected from the hospital database, while breastfeeding outcomes were obtained through telephone interviews. RESULTS: The mode of conception did not influence any of the breastfeeding outcomes. Breastfeeding duration was negatively affected by smoking. Vaginal delivery, birth weight > 2500 g, delivery > 37 gestational weeks, breastfeeding intention, and rooming-in are positively associated with the initiation of breastfeeding, while skin-to-skin contact and receiving information concerning breastfeeding are the most significant variables associated with its exclusivity and duration. CONCLUSIONS: The duration and exclusivity of breastfeeding are mainly related with information thereon, promotion, and breastfeeding support, but not with the mode of conception. It is essential to adequately support women from the outset in breastfeeding, as recommended by the World Health Organization (WHO) guidelines.

The Role of Staphylococcus aureus in Mastitis : A Multidisciplinary Working Group Experience.

BACKGROUND: Breastfeeding women are at risk of developing mastitis during the lactation period. Staphylococcus aureus has emerged as the community-acquired pathogen responsible for virulence (methicillin resistance and Panton-Valentine leukocidin toxin producing). RESEARCH AIM: The aim was to compare the microorganisms responsible for mastitis and breast abscesses during breastfeeding. METHODS: This observational study was conducted with a sample of women (N = 60) admitted to our hospital between 2016 and 2018. Participants affected by mastitis and breast abscess were studied and cared for by a multidisciplinary working group. A diagnostic breast ultrasound identified the pathology. RESULTS: Twenty-six participants (43.3%) were affected by mastitis and 34 (56.7%) by breast abscess. The most common microorganism identified was Staphylococcus aureus (S. aureus; mastitis, n = 13; abscesses, n = 24). Methicillin resistance was identified in 21 (44.7%) S. aureus strains: 17 (80.9%) cases of abscess and four (19.1%) cases of mastitis. The median number of months of breastfeeding was smaller in the methicillin-resistant S. aureus (MRSA) cases (median = 3, range = 1-20 months) than in the methicillin-sensitive S. aureus (MSSA) cases (median = 6.5, range = 3-21 months). The Panton-Valentine leukocidin toxin gene was detected in 12 (25.5%) cases (MRSA, n = 8, 66.7%; MSSA, n = 4, 33.3%). Hospitalization was required more frequently in MRSA (n = 8, 38%; five Panton-Valentine leukocidin positive) than in MSSA cases (n = 5, 19%; one Panton-Valentine leukocidin positive). Four women out of the eight MRSA cases (50%) that were Panton-Valentine leukocidin positive stopped breastfeeding during mammary pathologies, three (37.5%) participants continued breastfeeding until the follow-up recall, and one case was lost at follow-up. CONCLUSION: Clinical severity was probably complicated by the presence of the Panton-Valentine leukocidin toxin, which required hospitalization more frequently.

Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure.

Background: SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect un-treated depression. SSRIs undergo extensive hepatic first-pass metabolism with the involvement of several cytochrome P450 (CYPs) enzymes. Genetic polymorphisms may influence the expression and activity of CYPs genes. The first aim of this study was to evaluate neonatal outcomes in depressed mothers exposed to SSRIs during pregnancy. SSRIs pharmacogenetics was also evaluated in a subset of mothers and fetuses. Methods: In this case-control study, cases (n = 42) were Caucasian women with a diagnosis of depression and/or anxiety, treated with SSRIs for the whole pregnancy. Controls (n = 85) were Caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptics, drug of abuse, alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples were obtained at delivery to analyze genotype in 33 cases. Results: The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean hemoglobin values before delivery. Obstetric features were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be Low Birth Weight (LBW) (birth weight <2,500 g) (p = 0.01), had significantly lower mean Apgar scores at 1' (p = 0.006) and at 5' (p = 0.023) and worse Apgar distribution at 1' (p = 0.017) and at 5' (p = 0.013). Fifty-six percent of newborns presented one or more symptoms consistent with poor neonatal adaptation syndrome (PNAS). Pharmacogenetic analysis at delivery did not show significant differences in the frequencies of obstetric or neonatal complications in relation to polymorphisms. Conclusions: We found that newborns exposed to SSRIs are at increased risk of poor neonatal outcomes in terms of low birth weight, low Apgar scores and, clinically, poor neonatal adaptation syndrome. Preliminary pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence neonatal outcomes.

[Hepatic adenoma with high phlogosis indices: what relationship? Description of a pediatric clinical case.] / Adenoma epatico con alti indici di flogosi: quale relazione? Descrizione di un caso clinico pediatrico.

Hepatocellular adenoma is a benign neoplasm that accounts for 2-4% of pediatric liver tumors. The inflammatory variant of the adenoma can be expressed at the clinical level only with the evidence of persistent elevation of the inflammatory indices, since the hepatic mass is itself silent unless there are complications. The main complications relate to the bleeding risk, the chronic inflammatory state and the low risk of malignant evolution. The predictive marker of hemorrhagic complication is the size and in particular if the diameter is greater than 5 cm surgical treatment is recommended. We describe the case of a 9-year-old girl with a hepatocellular adenoma in the telangiectatic inflammatory variant, with a clinical presentation of loss of appetite and high inflammatory indices.

Placental ESRRG-CYP19A1 Expressions and Circulating 17-Beta Estradiol in IUGR Pregnancies.

Introduction: Sex steroids are regulating factors for intrauterine growth. 17-ß Estradiol (E2) is particularly critical to a physiological pregnancy, as increased maternal E2 was correlated to lower fetal weight at delivery. The placenta itself is a primary source of estrogens, synthetized from cholesterol precursors. Cytochrome P450 aromatase (encoded by CYP19A1 gene) is a rate-limiting enzyme for E2 biosynthesis. CYP19A1 transcription is supported by Estrogen Related-Receptor Gamma (ERRγ- ESRRG gene), which thus has an indirect role in placental steroidogenesis. Here we investigated maternal E2 levels and placental CYP19A1 and ESRRG expressions in pregnancies with IntraUterine Growth Restriction (IUGR). Methods: Singleton pregnancies were studied. E2 was measured in maternal plasma by electrochemiluminescence in 16 term controls and 11 IUGR (classified by umbilical artery doppler pulsatility index) at elective cesarean section, and also in 13 controls during pregnancy at a gestational age comparable to IUGR. CYP19A1 and ESRRG expressions were analyzed in placental tissue. Maternal/fetal characteristics, placental and molecular data were compared among study groups and tested for correlations. Results: Maternal E2 plasma concentrations were significantly decreased in IUGR compared to controls at delivery. When analyzing normal pregnancies at a gestational age similar to IUGR, E2 levels were not different to pathological cases. However, E2 levels at delivery positively correlated with placental efficiency. Placental CYP19A1 levels were significantly higher in IUGR placental tissue vs. controls, and specifically increased in female IUGR placentas. ESRRG expression was not different among groups. Discussion: We report a positive correlation between 17-ß Estradiol levels and placental efficiency, that might indicate a disrupted steroidogenesis in IUGR pregnancies. Moreover, we show alterations of CYP19A1 expression in IUGR placentas, possibly indicating a compensatory effect to the adverse IUGR intrauterine environment, also depending on fetal sex. Further studies are needed to deeper investigate IUGR alterations in the complex interaction among molecules involved in placental steroidogenesis.

Impact of Obesity and Hyperglycemia on Placental Mitochondria.

A lipotoxic placental environment is recognized in maternal obesity, with increased inflammation and oxidative stress. These changes might alter mitochondrial function, with excessive production of reactive oxygen species, in a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes. Here, we hypothesize that maternal pregestational body mass index (BMI) and glycemic levels can alter placental mitochondria. We measured mitochondrial DNA (mtDNA, real-time PCR) and morphology (electron microscopy) in placentas of forty-seven singleton pregnancies at elective cesarean section. Thirty-seven women were normoglycemic: twenty-one normal-weight women, NW, and sixteen obese women, OB/GDM(-). Ten obese women had gestational diabetes mellitus, OB/GDM(+). OB/GDM(-) presented higher mtDNA levels versus NW, suggesting increased mitochondrial biogenesis in the normoglycemic obese group. These mitochondria showed similar morphology to NW. On the contrary, in OB/GDM(+), mtDNA was not significantly increased versus NW. Nevertheless, mitochondria showed morphological abnormalities, indicating impaired functionality. The metabolic response of the placenta to impairment in obese pregnancies can possibly vary depending on several parameters, resulting in opposite strains acting when insulin resistance of GDM occurs in the obese environment, characterized by inflammation and oxidative stress. Therefore, mitochondrial alterations represent a feature of obese pregnancies with changes in placental energetics that possibly can affect pregnancy outcomes.

PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction.

Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR). We have evaluated utility and applicability of the PlGF test in a clinical setting of pregnancies at risk of PE or complicated by IUGR in order to assess its relationship with pregnancy outcomes. Seventy-three pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in relation to three categories of plasma PlGF levels: very low (<12 pg/ml), low (12-100 pg/ml) and normal (≥100 pg/ml). Uterine artery Doppler velocimetry (UADV) pulsatility index (PI) was measured in the same patients on the day of maternal sampling. Pregnancies at risk with very low plasma PlGF levels had significantly lower gestational age at delivery than patients with low or normal PlGF. The rate of emergency C-section was significantly higher in the group with PlGF <12 pg/ml. IUGR pregnancies with very low and low PlGF delivered earlier than patients with normal PlGF. All IUGR with very low and low PlGF had UADV PI > 95th percentile. Our data indicate that PlGF may provide useful information to identify fetuses requiring increased surveillance and possibly urgent delivery in pregnancies at risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse pregnancy outcomes that may be secondary to placental insufficiency.

Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children.

OBJECTIVE: The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi. SETTING: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam. PARTICIPANTS: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years). OUTCOMES: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG. RESULTS: The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative. CONCLUSIONS: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.

Sex specific adaptations in placental biometry of overweight and obese women.

INTRODUCTION: Placental biometry at birth has been shown to predict chronic disease in later life. We hypothesized that maternal overweight/obesity, a state of low-grade inflammation and risk factor for adverse pregnancy outcome, could negatively influence placental development and that differences would be sex-specific. METHODS: 696 women (537 normal-weight, NW; 112 overweight, OW; 47 obese, OB) with singleton uncomplicated pregnancies were prospectively enrolled at term delivery. Gestational age, maternal (age, height, pre-pregnancy BMI, gestational weight gain -GWG, hemoglobin, hematocrit and glycemia), fetal (weight, length, ponderal index, cranial circumference) and placental (weight, diameters) data were collected. Placental area, thickness and efficiency (fetal/placental weight ratio, F/P) were calculated. RESULTS: GWG was within standard recommendations in OB, while OW exceeded it. Placental weight was significantly higher in OW versus NW, but not in OB, leading to significantly higher placental thickness and lower F/P in this group. In the total population, a significant interaction effect between maternal BMI and fetal sex on placental weight and efficiency was found. Indeed, differences in placental parameters were present only in female offspring. DISCUSSION: In our population of OW and OB uncomplicated pregnancies only OW women, presenting GWG over standard recommendations, had thicker and less efficient placentas. We also reported different placental adaptation depending on fetal sex, with significant changes only in female fetuses. This may be part of a female-specific strategy aiming to ensure survival if another adverse event occurs. Customized counseling according to maternal BMI and fetal sex should be evaluated in clinical care.

Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension, preeclampsia, intrauterine growth restricted and normal pregnancies.

OBJECTIVE: Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the association between both maternal and fetal HLA-G 14 bp insertion/deletion polymorphism and obstetrical complications. METHODS: Clinical and genetic data of 282 women/fetuses (31 severe PE, 8 mild PE, 46 IUGR, 42 PIH and 155 controls) were analyzed both individually and jointly under a codominant, a dominant and a recessive model. RESULTS: HLA-G 14 bp polymorphism was not associated with obstetrical complications, considering the mother and fetus genotypes both jointly and individually. CONCLUSIONS: With this study we filled several gaps occurring in previous studies: we analyzed a very well-defined population of PE, PIH and IUGR pregnancies, considering both fetal and maternal HLA-G 14 bp polymorphism, individually and jointly. Our findings showed that fetal and maternal HLA-G 14 bp genotypes are not associated with increased risk for the development of obstetrical complications, suggesting that this polymorphism has no immuno-modulatory role in the development of PE, PIH or IUGR.