Neonatal hypoglycemia and neurodevelopmental outcomes: Yesterday, today, tomorrow.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches.   Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: • Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: • A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). • Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH.

Hammersmith Infant Neurological Examination in infants born at term: Predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. METHOD: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 37-43 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. INTERPRETATION: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.

EXAMEN NEUROLÓGICO INFANTIL DE HAMMERSMITH EN BEBÉS NACIDOS A TÉRMINO: SU USO PARA PREDECIR OTRAS CONDICIONES ADEMÁS DE LA PARÁLISIS CEREBRAL: OBJETIVO: Valoramos la capacidad del examen neurológico infantil de Hammersmith (HINE) para identificar el retraso en el rendimiento cognitivo a los 2 años en una cohorte grande de bebés nacidos a término. MÉTODO: Realizamos un estudio retrospectivo de bebés nacidos a término con riesgo de trastornos del desarrollo neurológico evaluados mediante el HINE entre los 3 y los 12 meses de edad postérmino y los comparamos con una cohorte de bebés nacidos a término con un desarrollo típico. Todos los bebés realizaron una evaluación del desarrollo neurológico a los 2 años de edad utilizando el Índice de Desarrollo Mental (MDI) de las Escalas de Desarrollo Infantil de Bayley, Segunda Edición; también se informó la presencia de parálisis cerebral (PC). Los bebés se clasificaron como cognitivamente normales/levemente con retreaso o significativamente con retraso (MDI < 70). La validez predictiva de las puntuaciones HINE para el rendimiento cognitivo con retraso significativo, en bebés con y sin parálisis cerebral, se calculó utilizando puntuaciones de corte específicas según la edad en la evaluación. RESULTADOS: Se incluyeron un total de 446 lactantes en riesgo y 235 con desarrollo normal (345 varones, 336 mujeres; edad gestacional media [DE] 38,7 semanas [1,4], rango de 37 a 43 semanas). De los lactantes en riesgo, 408 no tenían parálisis cerebral a los 2 años; 243 tenían un MDI con retraso normal/leve y 165 tenían un MDI inferior a 70. De los bebés en riesgo, 38 desarrollaron PC. Las puntuaciones HINE mostraron una buena sensibilidad y especificidad, principalmente después de 3 meses, para identificar un rendimiento cognitivo severo en lactantes sin PC. En aquellos con PC, la puntuación se asoció con su rendimiento cognitivo. El grupo de comparación tuvo las puntuaciones HINE más altas. INTERPRETACIÓN: El HINE proporciona evidencia sobre el riesgo de retraso en el rendimiento cognitivo a los 2 años de edad en bebés nacidos a término con y sin parálisis cerebral.

Hammersmith Infant Neurological Examination in low-risk infants born very preterm: a longitudinal prospective study.

AIM: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. METHOD: The HINE was performed at 3, 6, 9, and 12 months' corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. RESULTS: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23-31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. INTERPRETATION: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

Brain Growth Evaluation Assessed with Transfontanellar (B-GREAT) Ultrasound. Old and New Bedside Markers to Estimate Cerebral Growth in Preterm Infants: a Pilot Study.

OBJECTIVE: We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain Growth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). STUDY DESIGN: In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, and 7 of life, and then weekly until discharge, and at term) in preterm infants born with gestational age (GA) less than 32 weeks. We evaluated corpus callosum length, corpus callosum-fastigium length, anterior horn width, frontal white matter height, total brain surface, deep grey matter height, hemisphere height, transverse cerebellar diameter in the axial view, and transverse cerebellar diameter coronal view. Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. RESULTS: A total of 528 cranial ultrasounds were performed in 80 neonates (median birth GA: 28+5 weeks and interquartile range: 27+3-30+5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. CONCLUSION: B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates. KEY POINTS: · Overall neonatal brain growth is not routinely monitored using ultrasound.. · Old and new markers were used to build a standardized and non-invasive tool to monitor brain growth.. · All B-GREAT measurements had a good intra-observer and inter-observer agreement..

Hammersmith Infant Neurological Examination for infants born preterm: predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP). METHOD: We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months corrected age. At 2 years, cognition was assessed using the Mental Development Index (MDI; from the Bayley Scales of Infant Development, Second Edition) and the presence and severity of CP was determined. All children were classified as cognitively typical/mildly delayed or significantly delayed (MDI <70) and CP. The predictive validity of HINE scores for significantly delayed cognitive performance, in children with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: Of 1229 eligible infants (gestational age 25-36wks, mean [SD] 34.9 [2.3]; 646 males, 583 females), 1108 did not develop CP, 891 had an MDI that was typical/mildly delayed, and 217 had an MDI less than 70. Of the 121 infants who developed CP, the MDI was typical in 28, mildly delayed in 27, and less than 70 in 66. HINE scores showed a good sensitivity and specificity, especially after 3 months, for detecting significantly delayed cognitive performance in infants without CP. In those who developed CP, the score was associated with their cognitive level. INTERPRETATION: The HINE provides information about the risk of delayed cognitive performance in infants born preterm with and without CP. What this paper adds The Hammersmith Infant Neurological Examination (HINE) can be used in the first year to identify infants born preterm at risk for delayed cognitive performance. Age-dependent HINE cut-off scores are proposed for detecting increased risk of delayed cognitive performance.

A novel homozygous variant in JAM3 gene causing hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC) with neonatal onset.

BACKGROUND: JAM3 gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC). CASE REPORT: Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of JAM3 gene. CONCLUSION: Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a JAM3 variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels.

Ventriculosubgaleal shunt and neuroendoscopic lavage: refining the treatment algorithm of neonatal post-hemorrhagic hydrocephalus.

BACKGROUND: The optimal management of neonatal post-hemorrhagic hydrocephalus (PHH) is still debated, though several treatment options have been proposed. In the last years, ventriculosubgaleal shunt (VSgS) and neuroendosdcopic lavage (NEL) have been proposed to overcome the drawbacks of more traditional options, such as external ventricular drainage and ventricular access device. METHODS: We retrospectively reviewed neonates affected by PHH treated at our institution since September 2012 to September 2020. Until 2017 patients received VSgS as initial treatment. After the introduction of NEL, this treatment option was offered to patients with large intraventricular clots. After NEL, VSgS was always placed. Primary VSgS was reserved to patients without significant intraventricular clots and critically ill patients that could not be transferred to the operating room and undergo a longer surgery. RESULTS: We collected 63 babies (38 males and 25 females) with mean gestational age of 27.8 ± 3.8SD weeks (range 23-38.5 weeks) and mean birthweight of 1199.7 ± 690.6 SD grams (range 500-3320 g). In 6 patients, hemorrhage occurred in the third trimester of gestation, while in the remaining cases hemorrhage complicated prematurity. This group included 37 inborn and 26 outborn babies. Intraventricular hemorrhage was classified as low grade (I-II according to modified Papile grading scale) in 7 cases, while in the remaining cases the grade of hemorrhage was III to IV. Mean age at first neurosurgical procedure was 32.2 ± 3.6SD weeks (range 25.4-40 weeks). Death due to prematurity occurred in 5 patients. First-line treatment was VSgS in 49 patients and NEL in the remaining 14 cases. Mean longevity of VSgS was 30.3 days (range 10-97 days) in patients finally requiring an additional treatment of hydrocephalus. Thirty-two patients required one to three redo VSgS. Interval from initial treatment to permanent shunt ranged from 14 to 312 days (mean 70.9 days). CSF infection was observed in 5 patients (7.9%). Shunt dependency was observed in 51 out of 58 surviving patients, while 7 cases remained shunt-free at the last follow-up. Multiloculated hydrocephalus was observed in 14 cases. Among these, only one patient initially received NEL and was complicated by isolated trapped temporal horn. CONCLUSIONS: VSgS and NEL are two effective treatment options in the management of PHH. Both procedures should be part of the neurosurgical armamentarium to deal with PHH, since they offer specific advantages in selected patients. A treatment algorithm combining these two options may reduce the infectious risk and the risk of multiloculated hydrocephalus.

Therapeutic Hypothermia and Leukocytosis in Newborns: An Unusual Association.

Therapeutic hypothermia is a standardized intervention for the treatment of moderate-severe hypoxic-ischemic encephalopathy in newborns with gestational age ≥35 weeks. Several complications have been described. Our aim was to report a case of leukocytosis, for the first time in the literature, in a term newborn who underwent therapeutic hypothermia.

Joint Laxity in Preschool Children Born Preterm.

OBJECTIVE: To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally. STUDY DESIGN: The revised scale of Beighton Score was used to evaluate joint laxity in a population of 132 preschool children born preterm between 24 and 32 weeks of gestational age. All were assessed for joint laxity between 12 and 24 months of age. Children also performed the Movement Assessment Battery for Children-Second Edition between the age of 3 years and 6 months and 4 years; the age at onset of independent walking also was recorded. RESULTS: The total Beighton Score ranged between 0 and 8. Twenty percent of the cohort showed joint laxity. No differences related to sex or gestational age were observed. Children born preterm with joint laxity achieved later independent walking and achieved lower scores on Movement Assessment Battery for Children-Second Edition than those without joint laxity. In 76 children born preterm, an assessment for joint laxity was repeated once between 25 and 36 months and again after >36 months. No statistically significant difference was observed between the 3 assessments. CONCLUSIONS: The Beighton Score can be used to assess generalized joint laxity in children born preterm. As the presence of joint laxity influenced motor competences, the possibility to early identify these infants in the first 2 years is of interest to benefit from early intervention and potentially improve gross motor skills and coordination.

How to administrate erythropoietin, intravenous or subcutaneous?

AIM: To determine whether adding recombinant erythropoietin to the intravenous (IV) solution and administering it as a 24-h continuous infusion would result in an erythropoietic effect not inferior to that seen with subcutaneous (SC) administration. METHODS: Infants weighing ≤1500 grams and ≤32 weeks of gestational age were randomly assigned at 72 h of life to receive erythropoietin (300 units/kg, 3 times a week until 36 complete weeks of postmenstrual age or discharge), either subcutaneously [erythropoietin subcutaneous (ESC) group] or added to IV fluids [erythropoietin intravenous (EIV) group]. RESULTS: One hundred infants were randomized (50 in the EIV group and 50 in the ESC group). The incidence of transfusions was comparable in the two groups, similar in baseline characteristics and haematologic values at study entry. Phlebotomy losses did not differ between groups, and at the end of the study, there were no differences in reticulocyte counts, transferrin saturation and ferritin. No differences in the incidence of side effects were observed. CONCLUSIONS: In preterm infants, continuous intravenous administration of erythropoietin was not inferior to SC dosing.

Pravastatin for severe preeclampsia with growth restriction: Placental findings and infant follow-up.

OBJECTIVE: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided. STUDY DESIGN: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years. RESULTS: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls. CONCLUSIONS: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patients when pravastatin is administered in the late second trimester. However, we suggest its possible role in stabilizing the disease, increasing the prenatal weight gain and prolonging the duration of pregnancy, thus preventing the progression to a more severe maternal disease.

Conservative management of preterm premature rupture of membranes < 30 weeks of gestational age: Effectiveness of clinical guidelines implementation strategies.

Objective: To compare obstetrical and neonatal outcomes in patients with p-PROM (preterm premature rupture of membranes) at less than 30 weeks of gestational age before and after the application of protocols developed on the basis of international guidelines and to identify local barriers and strategies for their implementation. Study design: Single and twin pregnancies with p-PROM < 30 weeks of gestation without signs of infection were retrospectively collected. The population was divided in two groups. Group A contained patients treated before the introduction of the protocol, hospitalized from the day of the p-PROM to delivery and treated according to clinicians' practice. Group B included patients managed according to a standardized protocol, treated with home care management under strict surveillance, after 48 h of hospitalization. Results: 19 women with 21 newborns in group A and 22 women with 26 newborns in group B were enrolled. Maternal characteristics and p-PROM gestational age were comparable. In group A we observed minor latency time from diagnosis to delivery (1.6 vs 6.5 weeks, p < 0.001) with lower gestational age at delivery (25.8 ± 2 vs 30.7 ± 4.2 weeks, p = 0.00) and lower newborn weight (859 ± 268 vs 1511 ± 917 g, p = 0.002). Concerning neonatal outcomes, in group A there were lower Apgar score at 1 min (4.0 ± 2.1vs 6.3 ± 2, p = 004), longer hospitalization (42 ± 38 vs 68 ± 38 days, p = 0.05) and, even if non statistically significant, major rate of neonatal mortality (11,5% vs 19%, p = 1.00) and of neonatal complications (need of neonatal intensive care unit, sepsis, bronchopulmonary dysplasia, retinopathy of prematurity, mechanical ventilation). Postnatal follow-up showed comparable outcomes at 24 months of correct age. Conclusions: Educational and interdisciplinary meetings, along with group performance audit and standardization of procedures are successful strategies to implement guidelines application. Applying this strategy, we developed a protocol according to international guidelines for the treatment of early onset p-PROM based on a standardized conservative management at home, achieving better results compared to hospital management in terms of latency, gestational age at delivery, neonatal weight and neonatal hospitalization.

Sleep Disorders in Low-Risk Preterm Infants and Toddlers.

Sleep disorders are particularly important in the development of children, affecting the emotional, behavioural, and cognitive spheres. The incidence of these disorders has been assessed in different types of populations, including patients with a history of premature birth, who, from the literature data, would seem to have an increased incidence of sleep disorders at school age. The aims of the present study are: (i.) to assess the presence of sleep disorders in a population of very preterm infants at 6-36 months who are at low risk of neurological impairments using the Italian version of the Sleep Disturbance Scale for Children (SDSC) adapted for this age group, and (ii.) to identify possible differences from a control group of term-born infants. A total of 217 low-risk preterm and 129 typically developing infants and toddlers were included in the study. We found no differences in the SDSC total and the factor scores between these two populations of infants. Low-risk preterm infants and toddlers showed similar incidences of sleep disorders to their term-born peers. Further clinical assessments will be needed to confirm these data at school age.

pCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.

Background: Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants. Methods: This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system. Results: A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117). Conclusions: Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Neurologic assessment tool for screening preterm infants at term age.

The screening assessment tool of the Dubowitz neonatal neurologic assessment was adapted for preterm infants. The findings identified as "warning signs" in preterm infants were identical to those found in full-term infants, suggesting that this screening tool can also be used in preterm infants at term age.

Renal failure of the surviving fetus after intrauterine death of the co-twin.

Twin pregnancies are considered at a higher risk for fetal mortality than singleton pregnancies. The antenatal death of one of the twins is associated with an increasing rate of cerebral impairment and lesions in other organs in the surviving fetus, especially if the pregnancy is monochorionic. We describe a case of isolate renal failure becoming evident gradually after birth in a surviving twin after the antenatal death of the co-twin. Considering the deleterious effects of vascular disruption in a surviving twin, our findings suggest careful investigation of renal function, even if no intrauterine signs of diminished renal function were previously detected.

Spyramicine and Trimethoprim-Sulfamethoxazole Combination to Prevent Mother-To-Fetus Transmission of Toxoplasma gondii Infection in Pregnant Women: A 28-Years Single-center Experience.

BACKGROUND: There is weak evidence on the best treatment of pregnant women with Toxoplasma gondii infection to prevent the vertical transmission to the fetus. METHODS: We conducted a 28-year retrospective study aiming to compare the efficacy of three therapeutic regimens [Spiramicyn alone (Spy) vs. Pyrimethamine-Sulfadiazine (P/S) vs. Spiramicyn with Trimethoprim-Sulfamethoxazole (Spy+TMP-SMX)] for the prevention of mother-to-fetus transmission of T. gondii infection. RESULTS: 170 women were included: 58 (34.1%) had certain congenital toxoplasmosis (CT), 61 (35.9%) a probable infection and 41 (24.1%) possible infection. In total 97 mothers (57.1%) were treated with the Spy+TMP-SMX combination, 64 mothers (37.6%) were treated with Spy only and 8 mothers (4.7%) with P/S. Infected infants were 20/170 (11.7%). However, 8.2% (8/97) of infants born to mothers treated with Spy+TMP-SMX were infected, 20% (11/55) of infants born to women treated with Spy and 12.5% (1/8) of infants born to mothers treated with P/S were infected. Logistic regression analysis demonstrated that Spy treatment alone was associated with an increased risk of CT compared to the Spy+TMP-SMX combination (OR, 2.78, 95% CI 1.04-7.41, P value 0.041). No difference was observed when the Spy+TMP-SMX was compared with the P/S combination (OR 1.59; 95% CI 0.17 - 14.58; P value 0.682). Results were confirmed when the analyses were corrected by trimester of infection and by type of maternal treatment (OR 7.72; 95% CI 3.40-17.53, P value <0.001). CONCLUSIONS: The combination of Spy+TMP-SMX may be more effective in reducing the risk of maternal-fetal transmission of Toxoplasmosis compared to Spy alone; furthermore, this combination is not inferior to P/S, the current international standard-of-care maternal treatment for the prevention of CT. A prospective trial comparing the combination Spy+TMP-SMX with P/S would be necessary to provide definitive evidence on the best regimen for pregnant women with T. gondii infection.

Maternal Ureaplasma/Mycoplasma colonization during pregnancy and neurodevelopmental outcomes for preterm infants.

Introduction: Ureaplasma (U.) and Mycoplasma (M.) species have been related to pregnancy complications (including preterm birth) and worse neonatal outcomes. The aim of our work is to evaluate neurodevelopmental outcomes in preterm infants born to mothers with Ureaplasma/Mycoplasma colonization during pregnancy. Methods: Preterm infants with gestational age (GA) of ≤ 30 weeks were included in a retrospective follow-up study. To evaluate the effects of maternal vaginal colonization, we divided preterm infants into two groups: exposed and unexposed infants. All infants were assessed at 24 ± 3 months of age using Griffith's Mental Developmental Scales (GMDS). Results: Among 254 preterm infants, only 32 infants (12.6%) were exposed to U. /M. colonization during pregnancy. Exposed infants and unexposed ones had a similar Griffith's Developmental Quotient (106 ± 27.2 vs. 108.9 ± 19.5, respectively), without significant differences (p = 0.46). However, exposed infants had a significantly poorer outcome than their unexposed peers in terms of locomotor abilities (100.7 ± 28.3 exposed vs. 111.5 ± 26.1 unexposed, p = 0.03). Conclusion: For visual and hearing impairment, exposed and unexposed infants had similar incidences of cognitive and motor impairment. However, exposed infants had significantly lower locomotor scores than unexposed peers.

Neurodevelopmental Outcomes in Preterm Infants Receiving a Multicomponent vs. a Soybean-Based Lipid Emulsion: 24 Month Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Few studies in the literature have analyzed the long-term neurodevelopmental outcomes of the administration of a multicomponent versus a soybean-based lipid emulsion (LE) in preterm infants receiving parenteral nutrition (PN). A recent randomized controlled trial conducted in our unit provided evidence of better growth in head circumference during the hospital stay in those who received a multicomponent LE. METHODS: This is a 24 month follow-up study of preterm infants, previously enrolled in a randomized trial, who received a multicomponent LE (SMOFlipid®) or a standard soybean-based one (Intralipid®). We evaluated neurodevelopmental outcomes at 24 months of corrected age (CA) in the two groups. RESULTS: Ninety-three children were followed up to the age of 24 months CA. Due to the peculiar time frame of the SARS-CoV-2 pandemic, neurodevelopmental outcomes were evaluated only in 77 children: 37 in the SMOFlipid® group and 40 in the Intralipid® group. No differences in major disability rates or in Griffith's evaluation were found between the two groups. CONCLUSIONS: In our population study, the administration of a multicomponent LE containing fish oil, compared to a soybean-based LE, had no significant effects on neurodevelopmental outcomes in preterm infants at 24 months CA.

Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance.