Aim:To study the association between cue-based feeding (CBF) and growth trajectories and feeding characteristics up to two years of age. Methods:A retrospective cohort study of preterm infants born at 27⁰/₇-33⁶/₇ weeks' gestation across two feeding epochs [traditional feeding (TF) vs. CBF]. Anthropometric indices were assessed at discharge and during routine follow-up. Feeding characteristics at two years were assessed using the Montreal Children's Hospital Feeding Scale (MCHFS). Results:The cohort included 115 infants (TF n = 58; CBF n = 57). CBF was associated with a shorter length of stay (mean difference 11.8 days, p < 0.001) and earlier discharge (35.5 vs. 36.9 weeks' PMA, p < 0.001). Weight and head circumference Z-scores at discharge were comparable. Across follow-up, both groups demonstrated declines in weight- and length-for-age Z-scores, with consistently higher values in the TF group (weight: p = 0.004; length: p = 0.003). Total MCHFS scores and prevalence of feeding difficulties at two years were similar. However, coercive feeding behaviors were significantly more common in the TF group (p = 0.018 and p = 0.044). Conclusion:CBF was associated with earlier discharge and more adaptive parent-infant feeding interactions while supporting overall normal growth. Integrating responsive feeding with structured nutritional monitoring may optimize both somatic and relational outcomes in preterm infants.

Introduction: The aim of this study was to identify early metabolic alterations associated with intraventricular hemorrhage (IVH) and its complications, periventricular hemorrhagic infarction (PVHI), and post-hemorrhagic ventricular dilatation (PHVD), in very preterm infants. Methods: This population-based observational cohort included 7,313 preterm infants born at 24-32 weeks' gestation between 2009 and 2019. Twenty-one analytes were quantified from dried blood samples collected within the first 96 h of life using tandem mass spectrometry. Multivariable logistic regression models were used to examine the association between analyte concentration quartiles and IVH, including analysis stratified by IVH-related complications. Results: IVH was diagnosed in 882 infants, while 6,431 had normal neurosonography. Compared with infants in the lowest quartile, those in the highest quartile of methionine and proline concentrations had increased odds of IVH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.21-1.86 and OR 1.74, 95% CI: 1.40-2.17, respectively). In contrast, infants in the highest quartile of free carnitine concentrations had significantly lower odds of IVH (OR 0.53, 95% CI: 0.42-0.67). These associations were more pronounced among infants with PVHI (n = 149) and PHVD (n = 152) (p < 0.001). Conclusion: Among very preterm infants, higher methionine and proline concentrations within the first 96 h of life were associated with increased risks of IVH and its complications, whereas higher free carnitine concentrations were associated with lower risks. Whether these metabolic alterations reflect secondary responses to ischemic-hemorrhagic brain injury or act as modulators of germinal matrix vulnerability warrants further investigation.

Preterm-born infants face a heightened risk for socioemotional challenges. This study examined whether spontaneous movements in infancy predict social competence and self-esteem at early school age and whether motor skills and maternal emotional availability at early school age mediate these associations. One hundred six Israeli preterm-born infants (38.3% girls; 20.70% Arab) from middle-class families participated in the study. At Time 1, when infants were at the corrected age of 11-22 weeks (M = 14.5 weeks, SD = 2.14), their spontaneous movements were assessed. Time 2 took place at early school age (Mmonths = 89, SD = 13.75). Children's motor skills were evaluated using a standard test, and mothers' emotional availability was observed during mother-child play interactions. Mothers and teachers reported children's social competence, and teachers reported children's self-esteem. After controlling for child gender, gestational age at birth, and mothers' education level, the results indicated that atypical spontaneous movements in infancy predicted lower social competence and self-esteem in childhood. Motor skills in childhood mediated both links, and mothers' emotional availability mediated the link to social competence. These results highlight the significance of motor functioning in infancy and childhood for the socioemotional adjustment of preterm-born children. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

BACKGROUND:Establishing direct breastfeeding in preterm infants remains challenging in neonatal intensive care units (NICUs). While cue-based feeding (CBF) is considered a developmentally supportive approach, its impact on direct breastfeeding remains uncertain. METHODS:We conducted a retrospective cohort study of preterm infants born at 27 + 0 to 33 + 6 weeks' gestation and admitted to a single tertiary NICU. Infants were assigned to two distinct study epochs reflecting different feeding approaches: traditional feeding (TF) and a breastfeeding-supportive CBF approach. A washout period was applied to minimize contamination between epochs. The primary outcome was direct breastfeeding at discharge (at least once daily). Secondary outcomes included PMA at discharge, length of hospitalization, and growth parameters. Multivariable logistic regression was used to evaluate factors associated with direct breastfeeding at discharge. RESULTS:A total of 135 preterm infants were included (CBF n = 66, TF n = 69). Direct breastfeeding at discharge was more frequent in the CBF group than in the TF group (48.5% versus 23.2%, p = 0.002). CBF was independently associated with any direct breastfeeding at discharge (odds ratio [OR] 5.09; 95% confidence interval [CI] 2.02-12.82), after adjustment for maternal age and mode of delivery. Infants in the CBF group were discharged at a lower PMA and had a shorter hospitalization. Weight and head circumference z-scores at discharge were similar between groups, despite greater declines in z-scores during hospitalization in the CBF group. CONCLUSIONS:In this cohort of preterm infants, implementation of a breastfeeding-supportive CBF approach was associated with higher rates of any direct breastfeeding at discharge and shorter length of hospitalization, without differences in weight or head circumference z-scores at discharge. These findings suggest that a breastfeeding-supportive CBF approach may facilitate the establishment of direct breastfeeding in the NICU.

OBJECTIVES:To evaluate the clinical impact and adherence to the 2022 American Academy of Pediatrics guideline for neonatal hyperbilirubinemia in comparison with the 2004 guideline. METHODS:We conducted a retrospective study of all infants born at ≥ 35 weeks post-menstrual age during June-July from 2021 to 2023. Infants were categorised into two epochs: Epoch 1 (E1), treated according to the 2004 guidelines (2021-2022), and Epoch 2 (E2), treated according to the 2022 guidelines (2023). We assessed phototherapy rates, hyperbilirubinemia-related outcomes and non-adherence, defined as phototherapy treatment despite bilirubin levels > 2.0 mg/dL below the threshold. RESULTS:Among 4071 infants, 255 required phototherapy (183 in E1 and 72 in E2). The phototherapy rate decreased from 6.6% in E1 to 5.5% in E2 (p = 0.227). However, a significant increase in lack of adherence was observed in E2, with 47.2% receiving phototherapy below the threshold compared to 26.2% in E1 (p = 0.002). Infants in E2 underwent more skin-breaking procedures (p = 0.016) and had a higher rate of positive direct antiglobulin tests (p = 0.04). No differences were observed in the duration of phototherapy exposure, length of hospital stay or rate of readmissions. CONCLUSION:While adherence to guidelines was suboptimal, and rates of phototherapy did not significantly decline, a greater proportion of treated infants had hemolytic risk factors, suggesting more targeted use of phototherapy. Improved efforts are needed to enhance compliance with the guideline, which may in turn help minimise unnecessary interventions.

(Abstracted from JAMA Network Open 2024;7(2):e240146 A large portion of mortality in neonatal intensive care units (NICUs) can be attributed to genetic disorders and/or birth defects; often, diagnosis of specific disorders can be difficult due to overlapping symptomology and insufficient sensitivity of tests for this age group. Next-generation sequencing has the potential to provide precision diagnosis that will assist in prognosis, lifesaving therapy, and palliative care decisions and has been shown to be highly accurate.

Importance:National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective:To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants:This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures:Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results:A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance:In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Objective To examine the reliability of a novel ultrasound (US) method for assessment of endotracheal tube (ETT) position in neonates. Design Prospective, observational, single-centre, feasibility study. Setting Level III neonatal intensive care unit. Patients Term and preterm neonates requiring endotracheal intubation. Intervention US measurement of the ETT tip to right pulmonary artery (RPA) distance was used to determine ETT position according to one-fourth to three-fourths estimated tracheal length for weight. US demonstration of pleural sliding and diaphragmatic movement was also assessed. Chest radiography (CXR) was performed following each intubation. Main outcome measures Agreement between US assessment of ETT tip position and CXR served as the gold standard. Sensitivity, specificity, positive and negative predictive values for each US method and correlation between ETT tip to RPA distance on US, and ETT tip to carina distance on CXR were assessed. Results Forty-two US studies were performed on 33 intubated neonates. US evaluation of ETT-RPA distance identified 100% of ETTs positioned correctly: 77% deep and 80% high, demonstrating strong agreement with CXR (kappa=0.822). Sensitivity was 78%, specificity 100%, positive predictive value 100% and negative predictive value 86%. US ETT-RPA distance strongly correlated with CXR ETT-carina distance (r=0.826). No significant agreement was found between CXR and US assessment of pleural sliding and diaphragmatic movement. No adverse events were encountered during US scans. Conclusion US evaluation of ETT-RPA distance demonstrated excellent accuracy for determining ETT position in neonates compared with CXR. More research is needed to support its feasibility in clinical settings.

AimTo compare volume-driven and cue-based feeding of low birth weight preterm infants, regarding short-term outcomes, including transition to oral feeds, weight gain, and length of stay.MethodsThis was a retrospective cohort study. Feeding and weight gain outcomes were compared between infants fed by volume-driven and cue-based feeds. The groups were subdivided by birth weight categories.ResultsThe study group included 240 low birth weight preterm infants born before 34 weeks of gestation, 120 infants fed by volume-driven feeding were compared to 120 infants fed by cue-based feeding. The groups were sub-analyzed by birth weight categories: <1,500 g and 1,500–2,500 g. Study groups were comparable regarding baseline characteristics and neonatal morbidities. Infants fed by cue-based feeding were more likely to achieve full oral feeding faster and at an earlier gestational age. Infants with a birth weight <1,500 g were less likely to experience adverse respiratory episodes during cue-based feeding. Although the rate of weight gain was reduced in cue-based feeding in the heavier infant group, discharge weight, breastfeeding rates, and length of stay were comparable between the groups.ConclusionsCue-based feeding results in faster transition to full oral feeding in very low birth weight preterm infants and at an earlier gestational age.

Less invasive surfactant administration (LISA) involves delivering surfactant to a spontaneously breathing infant by passing a thin catheter through the vocal cords and has become the preferred method for surfactant delivery. However, the role of pre-LISA sedation remains unclear. The aim of this study was to describe the use of dexmedetomidine for LISA in preterm and early-term infants. This retrospective study evaluated preterm and early-term infants who received intravenous dexmedetomidine for LISA between December 2022 and March 2024. Primary outcomes included safety parameters such as the absence of bradycardia, hypotension, hypothermia, or respiratory depression, and the success rate of LISA, determined by the lack of endotracheal intubation within 72 h. Intergroup comparison based on a cutoff of 32 weeks post-menstrual age (PMA) was performed. Thirty-seven infants were included. The mean ± SD PMA at birth, birth weight, and age at LISA were 32.2 ± 2.7 weeks, 1879 ± 698 g, and 13.9 ± 12.4 h, respectively. Mean dexmedetomidine dosage was 0.66 ± 0.26 μg/kg. Six patients (16.2

ObjectiveTo determine the effect of perinatal and neonatal risk factors on retinopathy of prematurity (ROP) and to examine the association of fertility treatments on the risk for ROP in very low birth weight (VLBW) preterm twins.MethodsThe population-based observational study consisted of VLBW twins born at 24-29 weeks gestational age (GA). Data from the Israel national database (1995-2020) were applied. Univariate and multivariable logistic regression using the General Estimating Equation were used for assessment of risk factors.ResultsThe study population comprised 4092 infants of whom 2374 (58%) were conceived following fertility treatments. ROP was diagnosed in 851 (20.8%) infants. The odds for ROP approximately doubled with each week decrease in GA: at 24 weeks, Odds Ratio (OR) 58.00 (95% confidence interval (CI) 31.83-105.68); 25 weeks, OR 25.88 (95% CI 16.76-39.96); 26 weeks, OR 12.69 (95% CI 8.84-18.22) compared to 29 weeks GA. Each decrease in one birthweight z-score was associated with 1.82-fold increased risk for ROP (OR, 1.82, 95% CI 1.59-2.08). Infertility treatments were not associated with ROP. Neonatal morbidities significantly associated with ROP were surgical necrotizing enterocolitis (NEC) (OR, 2.04, 95% CI 1.31-3.19); surgically treated patent ductus arteriosus (PDA) (OR, 1.63, 95% CI 1.12-2.37); sepsis (OR, 1.43, 95% CI 1.20-1.71) and bronchopulmonary dysplasia (OR, 1.52, 95% CI 1.22-1.90).ConclusionAmong preterm VLBW twins, poor intrauterine growth and surgical interventions for NEC and PDA were associated with high odds for ROP. This study does not support an association of fertility treatments with increased risk for ROP.

Executive functions are a set of top-down cognitive processes necessary for emotional self-regulation and goal-directed behaviour supporting, among others, academic abilities. Premature infants are at high risk for subsequent cognitive, psychosocial, or behavioural problems even in the absence of medical complications and in spite of normal brain imaging. Given that this is a sensitive period of brain growth and maturation, these factors may place preterm infants at high risk for executive function dysfunction, disrupted long-term development, and lower academic achievements. Therefore, careful attention to interventions at this age is essential for intact executive functions and academic development.

Objective To examine associations between early exposure to mother's own milk (MOM) and neurodevelopmental outcomes among preterm infants, and to compare these associations between singletons and twins. Study design Retrospective cohort study that included low-risk infants born at <32 weeks gestational age. Nutrition was documented over a 3-day period at mean ages of 14 and 28 days of life; an average of the 3 days was calculated. The Griffiths Mental Development Scales (GMDS) were administered at 12 months corrected age. Results Preterm infants (n = 131) with median gestational age of 30.6 weeks were included; 56 (42.7%) were singletons. On days 14 and 28 of life, 80.9% and 77.1% were exposed to MOM, respectively. Exposure rate was comparable, but MOM intake (mL/kg/day) was higher among singletons than among twins (P < .05). At both time points, MOM-exposed infants scored higher on personal-social, hearing-language, and total GMDS assessments than nonexposed infants. These differences were significant for the entire cohort and for twins (P < .05). MOM intake correlated with total GMDS score for both singletons and twins. Any exposure to MOM was associated with additional 6-7 points on total GMDS score or 2-3 additional points for every 50 mL/kg/day of MOM. Conclusions The study supports the positive association between early MOM exposure among low-risk preterm infants and neurodevelopmental outcomes at 12 months corrected age. The differential effects of MOM exposure on singletons vs twins need further exploration. (J Pediatr 2023;259:113484).

Executive functions are a set of top-down cognitive processes necessary for emotional self-regulation and goal-directed behaviour supporting, among others, academic abilities. Premature infants are at high risk for subsequent cognitive, psychosocial, or behavioural problems even in the absence of medical complications and in spite of normal brain imaging. Given that this is a sensitive period of brain growth and maturation, these factors may place preterm infants at high risk for executive function dysfunction, disrupted long-term development, and lower academic achievements. Therefore, careful attention to interventions at this age is essential for intact executive functions and academic development.

Background Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. Methods This is a multicenter, matched case–control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. Results Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92–9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69–14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. −0.27 ± 0.97, OR = 2.03 (1.19–3.49), p = 0.01), longer duration of glucose infusion (3 (1–5) days vs. 2 (0–4), OR = 1.23 (1.03–1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32–20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11–0.88), p = 0.027). Conclusions A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. Impact Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Aim: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother’s breastmilk or to wait for breastmilk to be available. Methods: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012–2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported. Results: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group. Conclusion: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother’s breastmilk.

When assessing language development, it is important to differentiate between receptive language, namely comprehension, and expressive language, which is the ability to convey information, feelings, thoughts and ideas. The development of word comprehension and sensitivity to linguistic sounds occur before production.1 One study found that newborn infants were able to differentiate between a foreign language and their mothers' native language at an average of 32 h of life using different sucking frequencies.2 New challenges have arisen during the COVID19 pandemic, and questions have been raised about how social isolation and maskwearing have affected the language developmental trajectories of young infants. Facial expressions and gestures have played an important role in evolutionary history and have been associated with language acquisition.3 Humans rely on the way the mouth displays emotion. The extent to which the mouth is observed in proportion to the eyes may affect the child's ability to communicate in a typical way. Covering the mouth also eliminates the lipreading cues that enable infants to understand language,4 and slows down the neural processing of auditory speech signals. This has a detrimental effect on speech perception.4 The COVID19 pandemic has provided a unique opportunity to examine the importance of information generated from the face, and more specifically of the nose and mouth to a child's receptive and expressive language development up to the age of 12 months. We hypothesised that greater exposure to masks (i.e. longer exposure to masked individuals) would be related to reduced word production and comprehension skills. The cohort comprised 50 healthy term infants in a single tertiary medical centre in Israel from February to May 2020 (the first COVID19 wave). During this time window, the local Ministry of Health ordered major restrictions, including strict recommendations of maskwearing during every interaction with others, home lockdown and closures of the education systems. The parents all spoke Hebrew and were contacted by telephone when their infants were at mean age of 12.86 ± 1.78 months. Socioeconomic status was assessed, and the Hebrew version of the MacArthurBates Communicative Development Inventories for word production and comprehension were used at the time of recruitment. The questionnaires requested information about the last 3 months of their child’s life, about the child's primary carer, the number of adults and siblings the children were exposed to on an average day and the total time the infant was exposed to people wearing masks during an average day in the past month. The possible answers were never, rarely (up to 1 h), sometimes (2– 5 h), often (6– 8 h) and always (more than 9 h). These data were combined to create two subgroups: longer exposure to masks (2– 9 h) and shorter exposure to masks (0– 1 h). A twoway independent ttest analysis was conducted for word production and comprehension to determine differences in language comprehension and production between infants exposed to longer versus shorter mask duration. A Bonferroni correction was used to adjust the data for multiple comparisons. There were 16 infants (56% female) in the longer mask duration group and 34 (15% female) in the shorter mask duration group, and their demographics and characteristics are presented in Table 1. There was no difference in word comprehension between the shorter and longer mask duration groups (mean 135.56 ± 136.53 vs. 111.94 ± 71.81, t = 0.733, p = 0). However, infants exposed to shorter maskwearing produced significantly more words than the longer mask group (mean 17.21 ± 18.3 vs. 7.5 ± 5.07, respectively, t = 2.867, p < 0.01). Children who were exposed to masked caregivers for a longer time produced a significantly lower number of words. However, no differences were found in word comprehension levels between the two groups, disproving our hypothesis. The importance of combining visual and auditory information when acquiring language has been reported.5 The jaw, lips and tongue provide invaluable information when processing language,5 which may be even more important in the first year of life.5 Adult studies have shown that masks affected the quality of sound and prevented the important visual information perceived from the lips and tongue. It has been suggested that listening to masked individuals requires a greater cognitive load when processing linguistic information and this affects sentence recall. Babies initially process phonemes, which are visual cues that are coupled and synchronised with clear auditory signals. These are critical for processing and learning to produce new words. Our study had some limitations, including the relatively low number of participants, the use of selfreports for mask use and using questionnaires rather than actual performance tests. Another limitation was we could not test responses when the same children were exposed to masked and unmasked individuals.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

Objective: To evaluate whether early-onset severe preeclampsia prior to 34 weeks’ gestation is clinically different when associated with antiphospholipid antibodies. Design: A retrospective case-control study. Setting: Single university-affiliated tertiary referral center Population: 55 women with singleton pregnancies who delivered prior to 34 weeks’ gestation due to preeclampsia with severe features. Methods: Out of the 101 women with preeclampsia with severe features, the antiphospholipid antibodies status of 55 was available for analysis. The study group comprised 20 women with positive antiphospholipid antibodies (positive-aPL group), while the control group comprised 35 women without antiphospholipid antibodies (negative-aPL group). Main outcome measures: Obstetric and neonatal outcomes, laboratory results and pregnancy complications. Results: Positive-aPL women were hospitalized earlier (29, IQR 26.3–32, vs. 32, IQR 28-33 weeks gestation, p=0.05), gave birth at a significantly earlier gestational age (30, IQR 28.3-32.8 vs. 33, IQR 30-34, p=0.02) with a lower mean birth weight (1266.7±579.6 vs. 1567.3±539.7 grams, p=0.058) compared with negative-aPL women. Furthermore, platelet nadir was significantly lower for positive-aPL compared with negative-aPL women (97.2±49.7103/µL vs 141.3±61.13/µL, p<0.001) and maximal serum creatinine was higher (1.02±0.32 mg/dL vs. 0.92±0.13 mg/dL, p=0.03). Rates of neonatal complications were low and comparable between groups, although there was a trend for higher perinatal mortality among study group infants. Conclusions: The presence of antiphospholipid antibodies in women with early-onset preeclampsia with severe features is associated with earlier, more severe multi-organ involvement. Expedited screening for antiphospholipid antibodies in cases of early-onset severe preeclampsia may be considered.