Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation.

Fetal hydrops is a condition resulting from interstitial fluid accumulation in fetal compartments secondary to increased capillary permeability and characterized by high rates of perinatal mortality and morbidity. Clinical features include skin edema, hydrothorax, pericardial effusion, ascites with or without polyhydramnios, and placental edema. While it may occur as associated feature in multiple disorders, it has been documented to recur in Noonan syndrome, the most common disorder among RASopathies, but also in cardiofaciocutaneous and Costello syndromes. Here, we report on the occurrence of severe hydrops in a newborn heterozygous for the invariant c.4A>G missense change in SHOC2 which underlies Noonan-like syndrome with loose anagen hair, documenting that it represents a clinically relevant complication in this condition, shared by RASopathies.

Assessment of prenatal exposure to ethanol by meconium analysis: results of an Italian multicenter study.

BACKGROUND: This study estimated in 7 Italian cities the prevalence of prenatal exposure to ethanol by determining fatty acid ethyl esters (FAEEs; palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic esters) and ethyl glucuronide (EtG) in neonatal meconium samples. METHODS: A total of 607 meconium samples were obtained from neonatal wards of 7 public hospitals: Verona and San Daniele del Friuli in the northeast of the country, Reggio Emilia in the middle east, Florence and Rome in the center, and Naples and Crotone in the southwest of the peninsula. Meconium biomarkers were assessed by a validated methodology using liquid chromatography-tandem mass spectrometry and the results categorized using the accepted cutoff of 2 nmol/g total amount of 7 FAEEs and 2 nmol/g EtG, to differentiate between heavy maternal ethanol use during pregnancy and occasional or no use at all. RESULTS: On the basis of the above-reported cutoffs, the overall prevalence of newborns prenatally exposed to maternal ethanol was 7.9%: 0% in Verona, 4.0% in San Daniele del Friuli, 4.9% in Naples, 5.0% in Florence, 6.2% in Crotone, up to 10.6% in Reggio Emilia, and 29.4% in Rome. Low maternal education level and younger maternal age were associated with biomarker scores over the cutoff. There was also a significant correlation between the highest percentage of prenatal exposure in the capital and certain maternal sociodemographic characteristics. CONCLUSIONS: These results indicate considerable variability in the prevalence of fetal exposure to ethanol in different Italian cities, as determined by the objective measurement of biomarkers in meconium. These data, together with previous ones obtained in Barcelona, Spain, indicate that gestational ethanol exposure is widespread, at least in parts of Europe.

Severe acquired cytomegalovirus infection in a full-term, formula-fed infant: case report.

BACKGROUND: Cases of cytomegalovirus colitis are exceptionally reported in immuno-competent infant. The pathogenesis is uncertain but breast-feeding is considered as a main source of postnatal infection. CASE PRESENTATION: Here we report a full-term, formula-fed infant who developed a severe cytomegalovirus anaemia and colitis when aged 2 months. CONCLUSION: Even if the molecular identity between the cytomegalovirus-isolate of the infant and the maternal virus could not be demonstrated, we confirmed through laboratory investigation that cytomegalovirus infection was acquired postnatally. However, the source of cytomegalovirus infection remained unclear. Alternative modes of cytomegalovirus transmission are discussed.

Population Baseline of Meconium Ethyl Glucuronide and Ethyl Sulfate Concentrations in Newborns of Nondrinking Women in 2 Mediterranean Cohorts.

The detection of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in meconium has been investigated recently as an alternative to meconium fatty acid ethyl esters (FAEEs) measurement as an objective estimate of prenatal alcohol exposure, independent of maternal self-reporting. We report the results of the first study conducted to investigate the concentrations of EtG and EtS in meconium from newborns with and without intrauterine exposure to ethanol, defined by questionnaire and meconium FAEEs concentration. FAEEs, EtG, and EtS were quantified by liquid chromatography tandem mass spectrometry in meconium samples obtained from the Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (n = 80) and from the Hospital del Mar in Barcelona, Spain (n = 105). Median EtG and EtS values in meconium from newborns without intrauterine exposure to ethanol varied between 0.100 and 0.140 nmol/g and 0.010 and 0.020 nmol/g in Reggio Emilia and Barcelona samples, respectively. In meconium from newborns with uncertain prenatal ethanol exposure, the EtG median value was 0.160 nmol/g in the Italian cohort and 0.250 nmol/g in the Spanish one. The median EtS concentration was 0.020 in both cohorts. EtG and EtS median values in 5 meconium samples from newborns of heavily drinking mothers were 7.240 nmol/g and 0.033 nmol/g, respectively. A positive cutoff of 2.0 nmol/g for EtG yielded the best sensitivity and specificity (100%) to discriminate for true prenatal exposure to ethanol. It was not possible to establish a proper cutoff for EtS because of the low number of positive samples. Based on our results, meconium EtG can be proposed as an alternate biomarker for intrauterine alcohol exposure. In contrast to the 7 FAEEs, EtG is just one molecule that could be screened in meconium samples from all newborns by a simple, low-cost, easy-to-perform immunoassay, which can be routinely applied in neonatology wards for the early diagnosis of prenatal exposure to ethanol.

Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.

CONTEXT: Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants. OBJECTIVE: To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates. DESIGN, SETTING, AND PATIENTS: Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis. INTERVENTION: Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth). MAIN OUTCOME MEASURE: First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid. RESULTS: Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred. CONCLUSION: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN53107700.

Liquid chromatography with tandem mass spectrometric detection for the measurement of ethyl glucuronide and ethyl sulfate in meconium: new biomarkers of gestational ethanol exposure?

A liquid chromatography tandem mass spectrometric (LC-MS/MS) method with postcolumn addition of acetonitrile for the determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in meconium was developed and validated using pentadeuterated EtG and pentadeuterated EtS as internal standards. The analytes were extracted from the matrix by acetonitrile, concentrated by solid phase extraction, separated using a reversed-phase chromatographic column, and quantified within 9 minutes. Lower limits of quantification were 5 and 1 ng/g meconium for EtG and EtS, respectively. Calibration curves were linear from lower limits of quantifications to 500 ng/g, with a minimum r > 0.999. At 3 concentrations spanning the linear dynamic range of the assay, mean recoveries ranged between 78.7% and 96.8% for EtG and between 72.1% and 95.6% for EtS. Inaccuracy was better than 8.1%, with intra-assay and interassay imprecision better than 7.2% and 10.5%, respectively. Matrix effects (ion suppression/enhancement) were found to be negligible. The analytes of interest were stable at room temperature, at 4 degrees C, when exposed to 3 freeze-thaw cycles, and when stored at -20 degrees C for up to 6 months. This sensitive and specific method was used to assess the presence of these alcohol biomarkers in meconium samples from 2 different city cohorts.

Liquid chromatography-tandem mass spectrometry for fatty acid ethyl esters in meconium: assessment of prenatal exposure to alcohol in two European cohorts.

Fatty acid ethyl esters (FAEEs) in meconium emerged as a reliable, direct biological marker for establishing fetal exposure to ethanol. We developed an LC-MS/MS method for ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate using ethyl heptadecanoate as the internal standard. The analytes were extracted from meconium with hexane, followed by solid-phase extraction with aminopropyl-silica columns. Chromatography was performed on a C(8) reversed-phase column using water/isopropanol/acetonitrile (20:40:40, v/v/v) as a mobile phase. A triple quadrupole mass spectrometer that monitored the transitions in multiple reaction-monitoring mode was used for the detection of the analytes. Limits of quantification (LOQs) varied between 0.12 and 0.20 nmol/g. Calibration curves were linear from LOQs to 50 nmol/g for all analytes, with a minimum r(2)>0.99. At three concentrations spanning the linear dynamic range, mean recoveries ranged between 53.6 and 86.7% for the different analytes. The validated method was applied to analysis of meconium in newborns of two European cities. The two cohorts presented with different prevalence of gestational ethanol consumption during pregnancy.

Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial.

IMPORTANCE: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs. OBJECTIVE: Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied. DESIGN: An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010. SETTING: Thirteen Italian and New Zealand tertiary neonatal intensive care units. PARTICIPANTS: 743 VLBW neonates were assessed until discharge for development of NEC. INTERVENTION: Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates <1000 g at birth). MAIN OUTCOME MEASURES: ≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge. RESULTS: Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p < 0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred. CONCLUSIONS AND RELEVANCE: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings. TRIAL REGISTRATION: ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700.

Impact of perinatal practices for early-onset group B Streptococcal disease prevention.

BACKGROUND: Prevention of residual cases of neonatal group B streptococcus (GBS) early-onset disease (EOGBS) has become a goal in the past decade. This study is aimed at evaluating changes in the incidence of EOGBS over a 9-year period after the implementation of a screening-based approach and comparing 2 different protocols for managing healthy-appearing at-risk newborns (ARNs). METHODS: A screening-based strategy was introduced in Emilia-Romagna (Italy) in 2003. A prospective, cohort study was conducted from 2003 to 2011; culture-proven EOGBS cases were analyzed in 2 periods: period 1 (2003 to 2008) and period 2 (2009 to 2011). ARNs (≥35 weeks' gestation) were managed according to 2 different protocols: laboratory testing plus observation (period 1) was replaced with expectant observation alone (period 2). RESULTS: Ninety-one EOGBS cases were observed (incidence rate: 0.26/1000 live births). The incidence in full-term babies declined from 0.30 (period 1) to 0.14/1000 live births (period 2, P = 0.04). Recto-vaginal screening cultures in full-term mothers increased significantly from 10/45 (period 1) to 10/14 (period 2, P = 0.002). EOGBS was diagnosed earlier in ARNs than in not-at-risk newborns (mean age 5.5 versus 14.5 hours, P = 0.007). There were no differences in age at diagnosis irrespective of whether ARNs were managed with laboratory testing plus observation (mean 3.5 hours, period 1) or with expectant observation alone (mean 2.4 hours, period 2). CONCLUSIONS: When screening cultures were handled according to standard protocols, cases of EOGBS in full-term newborns simultaneously decreased. ARNs were diagnosed in a timely manner through both strategies. The clinical yield of laboratory testing was negligible.