Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

A pilot study to disentangle the infant gut microbiota composition and identification of bacteria correlates with high fat mass.

Background: At birth, the human intestine is colonized by a complex community of microorganisms known as gut microbiota. These complex microbial communities that inhabit the gut microbiota are thought to play a key role in maintaining host physiological homeostasis. For this reason, correct colonization of the gastrointestinal tract in the early stages of life could be fundamental for human health. Furthermore, alterations of the infant microbiota are correlated with the development of human inflammatory diseases and disorders. In this context, the possible relationships between intestinal microbiota and body composition during infancy are of great interest. Methods: In this study, we have performed a pilot study based on 16S rRNA gene profiling and metagenomic approaches on repeatedly measured data on time involving a cohort of 41 Italian newborns, which is aimed to investigate the possible correlation between body fat mass percentage (FM%) and the infant gut microbiota composition. Results and conclusion: The taxonomical analysis of the stool microbiota of each infant included in the cohort allowed the identification of a specific correlation between intestinal bacteria, such as Bifidobacterium and Veillonella, and the increase in FM%. Moreover, the analysis of the infant microbiome's metabolic capabilities suggested that the intestinal microbiome functionally impacts the human host and its possible influence on host physiology.

Pooling Strategies to Modify Macronutrient Content of Pasteurized Donor Human Milk.

Background: Donor human milk (DHM) is the recommended feeding for preterm infants when mother's own milk is unavailable or insufficient. DHM macronutrient's variability may have significant implications on preterm growth. Different pooling strategies could be used to improve the macronutrient content, facilitating the achievement of nutritional requirements of preterm. Objective: The aim was to compare the impact of random pooling (RP) and target pooling (TP) strategies on the macronutrient content of DHM and to identify which RP practice allows the achievement of a macronutrient composition as similar as possible to that achievable with TP. Methods: The macronutrient content of 1,169 single-donor pools was analyzed, and a TP strategy combining 2,3,4, or 5 single-donor pools was adopted. On the bases of single-donor pools' analyses, a simulation of 10,000 randomly selected pools for each configuration of donor considered and for different milk volume proportions was performed. Results: Regardless of the type of strategy and milk volume, as the number of donor per pool increases, the percentage of pools with a macronutrient content equal or higher than the reference values for human milk increases. Conclusion: When a TP strategy is not feasible, a RP strategy combining at least five donors should be performed to obtain a better macronutrient content of DHM.

Neonatal intestinal failure: Growth pattern and nutrition intakes in accordance with weaning from parenteral nutrition.

BACKGROUND: Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF. METHODS: Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning. RESULTS: We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P < 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039). CONCLUSION: Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.

Ethical Considerations Within the ESPGHAN Community.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital's EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

Don't Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants.

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Safety and efficacy of a probiotic-containing infant formula supplemented with 2'-fucosyllactose: a double-blind randomized controlled trial.

BACKGROUND: Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life. This study tested the safety and efficacy of a starter infant formula containing Limosilactobacillus (L.) reuteri DSM 17938 and supplemented with 2'-fucosyllactose (2'FL). METHODS: Healthy infants < 14 days old (n = 289) were randomly assigned to a bovine milk-based formula containing L. reuteri DSM 17938 at 1 × 107 CFU/g (control group; CG) or the same formula with added 1.0 g/L 2'FL (experimental group; EG) until 6 months of age. A non-randomized breastfed group served as reference (BF; n = 60). The primary endpoint was weight gain through 4 months of age in the formula-fed infants. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, stooling characteristics, adverse events (AEs), fecal microbiota and metabolism, and gut immunity and health biomarkers in all feeding groups. RESULTS: Weight gain in EG was non-inferior to CG as shown by a mean difference [95% CI] of 0.26 [-1.26, 1.79] g/day with the lower bound of the 95% CI above the non-inferiority margin (-3 g/day). Anthropometric Z-scores, parent-reported stooling characteristics, gastrointestinal symptoms and associated behaviors, and AEs were comparable between formula groups. Redundancy analysis indicated that the microbiota composition in EG was different from CG at age 2 (p = 0.050) and 3 months (p = 0.052), approaching BF. Similarly, between sample phylogenetic distance (weighted UniFrac) for BF vs EG was smaller than for BF vs CG at 3-month age (p = 0.045). At age 1 month, Clostridioides difficile counts were significantly lower in EG than CG. Bifidobacterium relative abundance in EG tracked towards that in BF. Fecal biomarkers and metabolic profile were comparable between CG and EG. CONCLUSION: L. reuteri-containing infant formula with 2'FL supports age-appropriate growth, is well-tolerated and may play a role in shifting the gut microbial pattern towards that of breastfed infants. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT03090360 ) on 24/03/2017.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Diagnostic approach to neonatal and infantile cholestasis: A position paper by the SIGENP liver disease working group.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Assessment of pregnancy dietary intake and association with maternal and neonatal outcomes.

BACKGROUND: Maternal dietary habits are contributors of maternal and fetal health; however, available data are heterogeneous and not conclusive. METHODS: Nutrient intake during pregnancy was assessed in 503 women with uncomplicated pregnancies, using the validated Food Frequency Questionnaire developed by the European Prospective Investigation into Cancer and Nutrition (EPIC-FFQ). RESULTS: In all, 68% of women had a normal body mass index at the beginning of pregnancy, and 83% of newborns had an appropriate weight for gestational age. Maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated with birth weight. GWG was not related to the pre-pregnancy BMI. EPIC-FFQ evaluation showed that 30% of women adhered to the European Food Safety Authority (EFSA) ranges for macronutrient intake. In most pregnant women (98.1%), consumption of water was below recommendations. Comparing women with intakes within EFSA ranges for macronutrients with those who did not, no differences were found in BMI, GWG, and neonatal or placental weight. Neither maternal nor neonatal parameters were associated with the maternal dietary profiles. CONCLUSIONS: In our population, maternal pre-pregnancy BMI, GWG, and placental weight are determinants of birth weight percentile, while no association was found with maternal nutrition. Future studies should explore associations through all infancy. IMPACT: Maternal anthropometrics and nutrition status may affect offspring birth weight. In 503 healthy women, maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated to neonatal birth weight. GWG was not related to the pre-pregnancy BMI. In all, 30% of women respected the EFSA ranges for macronutrients. Neither maternal nor neonatal parameters were associated with maternal dietary profiles considered in this study. Maternal pre-pregnancy BMI, GWG, and placental weight are determinants of neonatal birth weight percentile, while a connection with maternal nutrition profiles was not found.

COVID-19 pandemic in the neonatal intensive care unit: any effect on late-onset sepsis and necrotizing enterocolitis?

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Energy Expenditure, Protein Oxidation and Body Composition in a Cohort of Very Low Birth Weight Infants.

The nutritional management of preterm infants is a critical point of care, especially because of the increased risk of developing extrauterine growth restriction (EUGR), which is associated with worsened health outcomes. Energy requirements in preterm infants are simply estimated, so the measurement of resting energy expenditure (REE) should be a key point in the nutritional evaluation of preterm infants. Although predictive formulae are available, it is well known that they are imprecise. The aim of our study was the evaluation of REE and protein oxidation (Ox) in very low birth weight infants (VLBWI) and the association with the mode of feeding and with body composition at term corrected age. METHODS: Indirect calorimetry and body composition were performed at term corrected age in stable very low birth weight infants. Urinary nitrogen was measured in spot urine samples to calculate Ox. Infants were categorized as prevalent human milk (HMF) or prevalent formula diet (PFF). RESULTS: Fifty VLBWI (HMF: 23, PFF: 27) were evaluated at 36.48 ± 0.85 post-conceptional weeks. No significant differences were found in basic characteristics or nutritional intake in the groups at birth and at the assessment. No differences were found in the REE of HMF vs. PFF (59.69 ± 9.8 kcal/kg/day vs. 59.27 ± 13.15 kcal/kg/day, respectively). We found statistical differences in the protein-Ox of HMF vs. PFF (1.7 ± 0.92 g/kg/day vs. 2.8 ± 1.65 g/kg/day, respectively, p < 0.01), and HMF infants had a higher fat-free mass (kg) than PFF infants (2.05 ± 0.26 kg vs. 1.82 ± 0.35 kg, respectively, p < 0.01), measured with air displacement plethysmography. CONCLUSION: REE is similar in infants with a prevalent human milk diet and in infants fed with formula. The HMF infants showed a lower oxidation rate of proteins for energy purposes and a better quality of growth. A greater amount of protein in HMF is probably used for anabolism and fat-free mass deposition. Further studies are needed to confirm our hypothesis.

Adherence to the Mediterranean diet and body composition of breast-feeding mothers: the potential role of unsaturated fatty acids.

A paucity of evidence is available regarding the impact of diet's quality during pregnancy and lactation on the body composition of breast-feeding mothers. The purpose of the present study was to evaluate the association between maternal degree of adherence to the Mediterranean diet (MD) and body composition measures specifically those relating to body fat, in the lactation period. A cross-sectional study on healthy mothers of full-term babies has been conducted. At 30 ± 10 d after delivery, anthropometric measurements and body composition were assessed. A food frequency questionnaire was performed to compute the Italian Mediterranean Index (IMI) score as an index of adherence to the MD. Data related to pregnancy such as pre-pregnancy weight, gestational weight gain and morbidities were also collected. The 147 mothers included were categorised in IMI-1 (IMI score < 5; n 92) and IMI-2 (IMI score ≥ 5; n 55) groups. IMI-2 mothers showed higher daily energy, total carbohydrates, starch and fibre intakes than IMI-1. The dietary habits of IMI-2 mothers reflect the typical characteristics of MD: they consumed higher quantities of proteins and lipids of vegetal origin, higher amounts of monounsaturated and polyunsaturated fatty acids (PUFAs) and lower saturated to PUFAs ratio. The IMI-2 group showed lower absolute fat mass and fat mass index compared to IMI-1 [(20⋅2 ± 5⋅9) v. (22⋅9 ± 8⋅4) kg; P 0⋅036 and (7⋅5 ± 2⋅2) v. (8⋅5 ± 3⋅1) kg/m2; P 0⋅036, respectively], whereas body weight [(61⋅1 ± 8⋅0) v. (63⋅3 ± 9⋅2) kg] and body mass index [(22⋅4 ± 2⋅6) v. (23⋅3 ± 3⋅5) kg/m2] were similar. The degree of adherence to the MD during pregnancy and lactation is positively associated with lower maternal fat deposition in the breast-feeding period. The higher quality of dietary lipids, probably in synergy with the assumption of starchy carbohydrates and fibre, could influence maternal body fat.

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

The indirect calorimetry in very low birth weight preterm infants: An easier and reliable procedure.

OBJECTIVES: Preterm infants are at increased risk of developing extrauterine growth restriction, which is associated with worse health outcomes. The energy needs are not well known, as the measurement of resting energy expenditure (REE) using indirect calorimetry has critical issues when applied to infants. One of the main issues is the time required to obtain reliable data owing to the difficulty in keeping infants quiet during the entire examination. Thus, the aim of this study was to define the minimum duration of calorimetry to obtain reliable data. METHODS: The volume of oxygen consumption (VO2) and the volume of carbon dioxide production (VCO2) were recorded for a mean duration of 90 consecutive minutes. REE was calculated using a neonatal prototype calculator. We extracted data regarding VO2, VCO2, and REE at 10(T1), 20(T2), 30(T3), 40(T4), and 50(T5) minutes of steady state and compared these data to those of entire steady state period. RESULTS: Twenty-six very low birth weight preterm infants were evaluated at 36.58 ± 0.99 wk corrected age. Infants were appropriate for gestational age and clinically stable without comorbidities. There were no significant differences between mean VO2 and REE at T1 (8.26 ± 1.45 mL/kg to 57.80 ± 10.51 kcal/kg), T2 (8.15 ± 1.41 mL/kg to 56.87 ± 10.05 kcal/kg), T3 (8.04 ± 1.41 mL/kg to 56.32 ± 9.73 kcal/kg), T4 (8.05 ± 1.41 mL/kg to 56.07 ± 10.28 kcal/kg), and T5 (8.06 ± 1.55 mL/kg to 57.17 ± 11.62 kcal/kg), respectively, compared to steady state (8.13 ± 1.33 mL/kg to 56.77 ± 9.34 kcal/kg). The median values of VCO2 were significantly different only when T1 data were compared with other time slots (7.02 ± 1.02 mL/kg at steady state; 7.26 ± 1.23 mL/kg at T1; 7.13 ± 1.20 mL/kg at T2; 7.02 ± 1.19 mL/kg at T3; 6.85 ± 1.16 mL/kg at T4; 6.91 ± 1.24 mL/kg at T5). CONCLUSION: Twenty consecutive minutes in steady state condition are sufficient to obtain reliable data on REE in stable, very low birth weight infants.

Thrombin Generation in Preterm Newborns With Intestinal Failure-Associated Liver Disease.

Background and Aim: Intestinal failure-associated liver disease (IFALD) affects one-fifth of neonates receiving parenteral nutrition (PN) for more than 2 weeks. We aimed to define the effect of IFALD on hemostasis of preterm infants. Methods: This is an ancillary analysis of a prospective study aimed at defining coagulation in preterm infants. We included neonates exposed to PN (at least 14 days), in full-enteral feeding. We compared thrombin generation in the presence of thrombomodulin, defined as endogenous thrombin potential-ETP, PT, aPTT between infants with IFALD vs. those without (controls), at birth, and after 30 days. IFALD was defined as conjugated bilirubin ≥1 mg/dl. Results: We enrolled 92 preterm infants (32 IFALD; 60 controls). Cholestatic patients had a lower birthweight, longer exposure to PN, and longer hospitalization. Infants with IFALD showed longer median PT (12.8-vs.-12 sec; p = 0.02) and aPTT (39.2-vs.-36.5 sec; p = 0.04) than controls, with no difference in ETP. Conclusions: Despite prolonged PTs and aPTTs infants with IFALD had similar ETP than those without.

The Potential Effects of Human Milk on Morbidity in Very-Low-Birth-Weight Preterm Infants.

Improvements in quality of care have led to a significant reduction in mortality and morbidity in preterm infants, especially very-low-birth-weight (VLBW) infants [...].