Surface Cranial Ultrasound: The Natural Heir to X-Ray for the Screening of Skull Deformities in Infants.

PURPOSE: Volumetric tomography (3D-CT) is currently considered the gold standard for the diagnosis of craniosynostosis, but its use as the first-line examination for cranial deformities is a topic of debate, because of skull X-ray radiation and low sensitivity and specificity. Cranial ultrasound is an emerging noninvasive radiation-free alternative, but its diagnostic accuracy still needs confirmation. MATERIALS AND METHODS: The present prospective study included 350 infants with skull deformities, who underwent cranial ultrasound as the first-line examination, followed by 3D-CT if the echography results was positive or unclear. If the results were negative, infants underwent physical treatment and follow-up. To evaluate ultrasound reliability, we focused on cases that underwent both the index test and the gold standard and performed a double-blind comparison of the echography and 3D-CT results. RESULTS: Ultrasound documented patent sutures in 293 infants and 9 had inconclusive results. The 293 ultrasound-negative infants were followed clinically: all improved, except 28 that underwent 3D-CT. In all of these cases, 3D-CT confirmed the ultrasonography results (no false negatives). 48 infants showed premature suture closure and underwent 3D-CT: 47 were confirmed (true positive), 1 was false positive. The sensitivity was 100%, the specificity was 99.7%, the positive and negative predictive values were 97.9% and 100%, respectively, the accuracy was 99.7%, and the diagnostic test evaluation was conclusive. CONCLUSION: The study documented the high sensitivity and specificity of echography for the diagnosis of craniosynostosis in a referral center, with better results being achieved before 6 months of age. Major limitations are the loss of diagnostic significance as the child grows and the learning curve needed. The advantages are avoidance of radiation and chance to evaluate the brain at the same time.

Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study.

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.

Prevalence of anti-parvovirus B19 IgG and IgM and parvovirus B19 viremia in pregnant women in an urban area of Northern Italy.

Parvovirus B19 (B19V) infection in pregnancy is mostly asymptomatic, but can cause complications including abortion and fetal hydrops. Although its infection is ubiquitous, seroprevalence among pregnant women varies according to different geographical areas. Since seroprevalence data in Italy are limited, the prevalence of antibodies and DNA in pregnant women was evaluated retrospectively, correlating the clinical situation of mothers and newborns. One thousand eight hundred and ninety-three sequential sera were examined from pregnant women (60.8% in the first trimester, 16.6% in the second one, and 22.6% in the third one, respectively) for anti-B19V IgG and IgM (confirmed by immunoblot); 1402 (74.1%) were of Italian origin and 491 (25.9%) non-Italian women. Molecular tests were used to search for viral genome. One thousand three hundred and fifteen (69.5%) samples were IgG-positive, 21 (1.1%) IgM-positive, and 578 (30.5%) nonimmune. The difference in IgG seroprevalence between Italian (71.1%) and non-Italian women (64.8%) was statistically significant. Of the 21 IgM-positive women, 16 were confirmed positive also by immunoblot (prevalence: 0.8%), of which 11 were viraemic (prevalence: 0.6%; mean 1.3 × 104 geq/ml). Mothers were asymptomatic, and the newborns had no clinical signs of congenital infection. IgG seroprevalence in Italy is high, with differences between Italian women and non-Italian women from geographic areas with lower endemic levels of B19V. The consistent migratory flows in place could lead to an increase in the number of susceptible women. The prevalence of viremia is low, and has not been associated with evident fetal damage at birth.

First Year Metabolic and Hormonal Behavior Define two Different Populations of SGA Newborn for Weight or Height.

Context: Small-for-gestational-age (SGA) children have a particular metabolic and hormonal pattern at birth that changes rapidly. Objective: To evaluate the linear and weight growth in the first year of life in SGA children. Design: Prospective, monocentric cohort study. Setting: Real-world data collected from April 2012 to January 2016. Patients: SGA newborns uniformly defined by either growth or length lower than -2 SDs for gestational age. Interventions: All children were evaluated for 1 year after birth, at 3 days of life, then 3, 6, and 12 months after birth. Main outcome measures: Anthropometric parameters and biochemical variables, such as blood glucose, insulin, leptin, IGF-1, IGF binding protein-3 (IGFBP-3), and homeostasis model assessment - insulin resistance (HOMA-IR) index. Results: A total of 133 SGA children were enrolled. Length significantly improved 1 month after birth, whereas weight significantly increased only at 3 months after birth. Biochemical variables increased during the first year of life, showing a prediction by IGFBP-3 and HOMA-IR index. Then, the variables were divided considering either weight, length, or both, showing a different incidence. The biochemical variable changes recorded in the first step were maintained considering SGA children for weight or length, whereas they disappeared when weight and length were considered together. Conclusions: Our study shows a specific catchup growth for weight and length in SGA children. Moreover, we highlight that weight and length should be considered as independent parameters in SGA children, defining 2 different metabolic-hormonal populations with different conceivable predictive role in early catchup growth and in later growth and metabolic status.

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.

Selective serotonin reuptake inhibitors' passage into human milk of lactating women.

Objective: Selective serotonin reuptake inhibitors are commonly used for the treatment of pregnancy-related and postnatal depression. However, only a few studies have evaluated the passage of these drugs into human milk, often with conflicting results. Here, we sought to evaluate the passage of selective serotonin reuptake inhibitors into human milk in the first days after delivery and their potential association with neonatal outcomes. Study design: The passage of selective serotonin reuptake inhibitors into human milk was expressed both as percentage of milk-to-plasma ratio of drug concentrations and as the relative infant dose (RID). Selective serotonin reuptake inhibitors were quantified by high-performance liquid chromatography combined with mass spectrometry. Results: Nineteen women treated with selective serotonin reuptake inhibitors during the third trimester of pregnancy and lactation were considered. Human milk-to-plasma ratios ranged from 51.1% to 703.4%. The patients had a median RID of 1.5%, with differences among the selective serotonin reuptake inhibitors. All newborns had been breastfed from birth up to day three of life. At 1 week follow up, 58% of infants were breastfed, 37% were complementary fed, and 5% were formula fed. No side effects due to passage of selective serotonin reuptake inhibitors into human milk were found. Conclusions: Selective serotonin reuptake inhibitors were detected in human milk, with milk-to-plasma ratios which in some cases exceeded 100%. Given the need for maternal therapy and the low incidence of neonatal adverse events, it is advisable not to preclude breastfeeding a priori but recommend it with careful follow-up.

Pharmacokinetics and Pharmacogenetics of Selective Serotonin Reuptake Inhibitors During Pregnancy: An Observational Study.

BACKGROUND: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. METHODS: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses. RESULTS: Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway. CONCLUSIONS: Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn.

Cerebral ultrasound abnormalities in offsprings of women with C677T homozygous mutation in the MTHFR gene: a prospective study.

BACKGROUND: Perinatal stroke is a common cause of neurologic disability. Being clinically under-recognized, its true incidence is not known. Maternal thrombophilia is likely to be a predisposing factor. To date, a general consensus for evaluation of babies born to mothers with genetic thrombotic predisposition is missing. This study was undertaken to assess the frequency of cerebral abnormalities in the offspring of women with homozygous C677T mutation in the MTHFR gene, and to seek for association with additional maternal or pregnancy risk factors. METHODS: Mother-infant pairs were consecutively recruited from October 2006 through February 2013. Neonates underwent a thorough physical examination at birth, and a cerebral ultrasound examination (cUS) was performed within 24 hours of their life. In neonates with major cerebral lesions, a thrombophilia panel test was obtained. Follow-up cUS was performed in babies with major or minor cerebral abnormalities. RESULTS: Ninety-one neonates (47 males) were enrolled. By cUS, abnormalities were detected in 18 (19.8%) neonates. Twelve neonates were diagnosed with a minor lesion; a major ischemic/hemorrhagic lesion was found in 6 neonates. There were a neat male preponderance and significant associations with a history of suspected miscarriage, maternal coagulation factors gene mutations, and reduced protein S or protein C activity. CONCLUSIONS: Our data confirmed a high incidence of cerebral abnormalities in neonates born to women with C677T homozygous mutation in the MTHFR gene. cUS at birth proved to be an effective screening tool or a diagnostic test, that should be routinely performed in babies born to mothers with known thrombotic predisposition.

Serotonin reuptake inhibitors in pregnancy: can genes help us in predicting neonatal adverse outcome?

Lots has been written on use of SSRI during pregnancy and possible short and long term negative outcomes on neonates. the literature so far has described a various field of peripartum illness related to SSRI exposure during foetal life, such as increased incidence of low birth weight, respiratory distress, persistent pulmonary hypertension, poor feeding, and neurobehavioural disease. We know that different degrees of outcomes are possible, and not all the newborns exposed to SSRIs during pregnancy definitely will develop a negative outcome. So far, still little is known about the possible etiologic mechanism that could not only explain the adverse neonatal effects but also the degree of clinical involvement and presentation in the early period after birth. Pharmacogenetics and moreover pharmacogenomics, the study of specific genetic variations and their effect on drug response, are not widespread. This review describes possible relationship between SSRIs pharmacogenetics and different neonatal outcomes and summarizes the current pharmacogenetic inquiries in relation to maternal-foetal environment.

Deformational plagiocephaly at birth: an observational study on the role of assisted reproductive technologies.

BACKGROUND: Following the "back to sleep" recommendations, a striking rise in deformational plagiocephaly (DP) occurred. However, additional maternal, pregnancy and infant conditions may play a role. OBJECTIVES: We aimed to evaluate the prevalence of and risk factors for DP at birth. Additionally, given the association between assisted reproductive technologies (ART) use and unfavorable pregnancy events, we explored the association between ART and DP. PATIENTS AND METHODS: A total of 413 neonates >33 weeks born at L. Sacco Hospital (Milan, Italy) from May 2011 through to January 2012 were enrolled. Data regarding parental, conceivement, pregnancy and delivery characteristics were recorded. Infants' skull measurements, including the oblique cranial length ratio (OCLR) were taken within 72 h after birth. Plagiocephaly was defined for OCLR > 105.9. RESULTS: The prevalence of DP was 20.3%. It was associated with twinning (OR 5.0; 95%CI 2.22-11.1), pregnancy complications (OR 2.86; 95%CI 1.49-5.26), prematurity (OR 2.13; 95%CI 0.98-4.54), ART use (OR 2.00; 95%CI 0.90-4.35) and male gender (OR 1.79; 95%CI 0.94-2.50). Adjusting for multiple pregnancies however, the association between ART and DP disappeared. CONCLUSION: Results show that offspring of pregnancies conceived through ART do not have increased risk of DP. However, our numbers are small thus larger studies are needed for definitive conclusions.

Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine.

A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity.

Longitudinal changes of bone ultrasound measurements in healthy infants during the first year of life: influence of gender and type of feeding.

There is evidence suggesting that early events in life may predispose the adult to osteoporosis. We assessed bone status by quantitative ultrasonography in healthy neonates, and we report the changes occurring during the first year of life, according to the type of early feeding. We measured the speed of sound (SOS) of the left tibia in 116 full-term infants (0-9 days of age) and in their mothers (21-42 years of age). SOS values did not correlate with gestational age of the study subjects (r = 0.08) or anthropometric measurements. The SOS measurements of the mothers did not correlate with those of their children (r = 0.01). Fifty-seven infants had SOS measurements performed at 4 and 12 months. Twenty-five infants were exclusively breast-fed, 12 received formula milk from birth, and 20 received human and formula milk. SOS measurements at 4 months were comparable with those at baseline, whereas at 12 months they were significantly higher. No effect of type of feeding was observed, indicating that SOS changes may be independent of the type of early diet.

Positional plagiocephaly: what the pediatrician needs to know. A review.

INTRODUCTION: Positional or deformational plagiocephaly is the most common type of cranial asymmetry in infancy and has become more prevalent after the introduction of the "Back to Sleep" campaign in Western countries. However, the supine position cannot be considered as the only etiologic factor and different predisposing variables have been investigated in the last few years. DISCUSSION: The pediatrician should correctly diagnose this condition and exclude the possibility of craniosynostosis in any child with plagiocephaly in order to optimize management and reduce potential morbidity associated with different conditions other than positional ones. In addition, the pediatrician needs to be able to educate parents on methods to proactively decrease the likelihood of the development of occipital flattening, initiate appropriate management, and make referrals when necessary.

Morbidity rates in late preterms born to HIV-mothers.

The rate of late preterm delivery has increased in the general population, and the late preterm infants have a higher incidence of morbidity compared to term newborns. Late preterm data are lacking in born to HIV-infected mother. We showed that, among 202 live births, late preterm delivery was higher in born to HIV-infected mothers than in the general population while their morbidity was lower.

Headache in children and adolescents aged 6-18 years in northern Italy: prevalence and risk factors.

OBJECTIVE: Aim of this study is to examine the epidemiology of paediatric headache and periodic syndromes in a school population and to evaluate the co-existence of environmental predisposing conditions. DESIGN AND METHODS: A 60-item questionnaire was completed by a school-based sample (n = 1536, ages 6-18 years). Diagnostic assessment of primary headache and periodic syndromes was established in first section; predisposing conditions in the second section; while the third section quantified the frequency of self medication and identified drugs most frequently used. RESULTS: Headache was reported by 62.1% of subjects. Socioeconomic status, composition of family unit and nutrition habits in the first year of life did not appear significantly different in subjects with headache compared to healthy controls. A good sleep quality was found in 95.2% of healthy controls, in 89.4% of children with occasional headache. Recurrent abdominal pain, motor weakness and car sickness was significantly higher in primary headache group compared to occasional headache. Depressive/anxious traits were significantly higher in primary headache and occasional headache groups than in healthy controls. The frequency of aggressive traits was also higher in children with primary headache compared to occasional headache and healthy control subjects. 72.5% of subjects with primary headache and 58.4% of children with occasional headache assumed medicines to relieve pain. Paracetamol was the most frequently assumed drug. CONCLUSIONS: Our data show a more frequent occurrence of anxious/depressive profile in children suffering from primary headache. In agreement with literature data, this research points out that self-treatment is a relevant problem in paediatric headache.

Maternal methylenetetrahydrofolate reductase (MTHFR) homozygosity and neonatal outcome: follow-up of 42 pregnancies at risk.

From February 2006 to March 2008, 42 pregnant women homozygous for the 677CT-methylenetetrahydrofolate reductase (MTHFR) allele were recruited in our obstetrics service for pregnancy at risk. All had antithrombotic prophylaxis with low-dose aspirin and/or low-molecular-weight heparin, supplemented with folic acid. In all, 2 women lost the fetus and 4 were lost to follow-up before delivery. A total of 36 women delivered term infants who all underwent transfontanellar ultrasonography within 24 hours of birth. Six (16.6%) had ischemic or hemorrhagic cerebral lesions. No differences were observed in gestational age, birth weight, or umbilical cord pH between the 30 healthy infants and the 6 with cerebral lesions. Neonatal outcomes were negative in spite of maternal folic acid supplementation and antithrombotic prophylaxis during pregnancy. This suggests a relationship between maternal homozygous mutation in the 677CT-MTHFR allele and neonatal cerebral lesions.