Epidemiology of congenital heart defects in France from 2013 to 2022 using the PMSI-MCO (French Medical Information System Program in Medicine, Surgery, and Obstetrics) database.

BACKGROUND: Congenital heart defects are common and occur in approximately 0.9% of births. In France, the registries cover approximately 20% of the population but not the entirety of France; therefore, we aimed to update the incidence data for congenital heart defects in France from 2013 to 2022 using the medico-administrative database PMSI-MCO (French Medical Information System Program in Medicine, Surgery, and Obstetrics). We aimed to compare the frequency of risk factors in a population with congenital heart defects and a reference population. METHODS: From 2013 to 2022, we included children aged < 3 years diagnosed with congenital heart defects according to the International Classification of Diseases, 10th Revision, in the PMSI-MCO database. We compared them with a population without congenital defects on several medical data items (e.g., parity, gemellarity, and mortality rate). Bivariate and multivariate analyses compared children with congenital heart defects and children without congenital malformation. RESULTS: We identified 83,879 children with congenital heart defects in France from 2013 to 2022 in the PMSI-MCO database and 7,739,840 children without such defects, including 7,218,952 without any congenital defects. We observed more deaths (7.49% vs. 0.68%, d = 0.59) and more twinning (8.67% vs. 1.23%, d = 0.35) among children with congenital heart defects. Multivariate analysis revealed an increased risk of congenital heart defects in male individuals (OR [odds ratio] 1.056, 95% CI [confidence interval] [1.039-1.076]) and cases of medically assisted reproduction (OR 1.115, 95% CI [1.045-1.189]) and a reduced risk in the case of multiparity (OR 0.921, 95% CI [0.905-0.938]). CONCLUSIONS: According to the PMSI-MCO database, the incidence of congenital heart defects in France from 2013 to 2022 is 1% of births. Congenital heart defects are more frequent in cases of prematurity, twinning, primiparity, male sex, and maternal age > 40 years.

Efficiency and Impact of Hypnoanalgesia for Cardiac Catheterisation in Paediatric Population.

Hypnoanalgesia is a promising non-pharmacologic adjunct technique in paediatric interventions. Its safety, efficiency, and impacts on paediatric cardiac catheterisation (CC) are unknown. METHODS: In a prospective study, patients aged <16 years who underwent CC under hypnoanalgesia from January to December 2021 were included. Pain and anxiety were assessed using the analgesia nociception index (ANI) and the visual analogue scale (VAS). RESULTS: Sixteen patients were included; the mean age was 10.5 years, and the mean weight was 37 kg. Catheterisations were interventional in 10 patients (62.5%). Hypnoanalgesia indications were general anaesthesia (GA) contraindication in four patients (25.0%), the need for accurate pressure measurements in three patients (18.7%), and interventionist/patient preferences in nine (56.3%). CC was accomplished in 15 patients (93.7%), even in complicated cases. In one case, pulmonary artery pressures were normalised compared to previous catheterisation under local anaesthesia alone. The VAS score was under 5/10 for all patients. The ANI remained above 50 (no painful zone) for all but one patient. There was no significant decrease in the ANI during the intervention compared to the baseline (p = 0.62). No complications were reported. CONCLUSION: Paediatric CC is feasible and safe under hypnoanalgesia, even in complicated cases. Hypnoanalgesia was efficient in managing pain and stress, and it ensures more reliable pressure measurements.

Effect of delayed cord clamping on red blood cell alloimmunization: a retrospective cohort study.

BACKGROUND: Although delayed cord clamping has well-known benefits for preterm and term neonates, it has been inadequately assessed in alloimmunized neonates. OBJECTIVE: This study aimed to evaluate the benefits and risks of delayed cord clamping in alloimmunized neonates. STUDY DESIGN: This was a retrospective comparative pre-post cohort study conducted from 2003 to 2018 in a tertiary care center in France. All living singleton neonates whose mothers were followed up for red blood cell alloimmunization during gestation and confirmed at birth (N=224) were included. Neonates were either exposed to immediate (n=125) or delayed cord clamping (n=99). Our main outcome was the time from birth to first exchange transfusions and/or transfusions. Secondary outcomes were hemoglobin level at birth, rate of exchange transfusion, number of postnatal transfusions, maximum bilirubin level, and number of phototherapy hours. RESULTS: Hemoglobin at birth was significantly higher in case of delayed cord clamping (mean difference, 1.7 g/dL; 95% confidence interval, 0.7-2.8). Among infants treated with exchange transfusion or transfusion, the time to initial treatment was higher in case of delayed cord clamping (median difference, 8 days; rate ratio, 1.51; 95% confidence interval, 1.09-2.10). There were no significant differences in the need for exchange transfusion, the number of transfusions, the maximum total bilirubin level, nor the number of phototherapy hours. In the subgroup analysis of neonates needing intrauterine transfusion during pregnancy (ie, severe alloimmunization), neonates had a lower rate of exchange transfusion in case of delayed cord clamping (odds ratio, 0.36; 95% confidence interval, 0.15-0.82). CONCLUSION: Our results indicate a benefit of delayed cord clamping in alloimmunization, regardless of pathology severity, without increased risk of jaundice.

Diastolic ventricular function in persistent pulmonary hypertension of the newborn.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is usually considered a consequence of impaired pulmonary circulation. However, little is known regarding the role of cardiac dysfunction in PPHN. In this study, we hypothesized that the tolerance for pulmonary hypertension in newborn infants depends on the biventricular function. The aim of this study is to evaluate biventricular cardiac performance by using Tissue Doppler Imaging (TDI) in an healthy newborn infants with asymptomatic pulmonary hypertension and in newborn infants with PPHN. Methods: Right and left cardiac function were investigated using conventional imaging and TDI in 10 newborn infants with PPHN ("PPHN") and 10 asymptomatic healthy newborn infants ("asymptomatic PH"). Results: Systolic pulmonary artery pressure (PAP) as assessed by TDI and the mean systolic velocity of the right ventricular (RV) free wall were similar in both groups. The isovolumic relaxation time of the right ventricle at the tricuspid annulus was significantly longer in the "PPHN" than in the "asymptomatic PH" group (53 ± 14 ms vs. 14 ± 4 ms, respectively; p < 0.05). Left ventricular (LV) function was normal in both groups with a systolic velocity (S'LV) at the LV free wall groups (6 ± 0.5 cm/s vs. 8.3 ± 5.7 cm/s, p > 0.05). Conclusion: The present results suggest that high PAP with or without respiratory failure is not associated with altered right systolic ventricular function and does not affect LV function in newborn infants. PPHN is characterized by a marked right diastolic ventricular dysfunction. These data suggest that the hypoxic respiratory failure in PPHN results, at least in part, from diastolic RV dysfunction and right to left shunting across the foramen ovale. We propose that the severity of the respiratory failure is more related to the RV diastolic dysfunction than the pulmonary artery pressure.

Pre-gestational diabetes and the risk of congenital heart defects in the offspring: A French nationwide study.

AIM: To compare the frequencies and types of congenital heart defects for infants of women without and with pre-gestational diabetes, type 1 and type 2 diabetes (T1DM, T2DM) and to identify risk factors. METHODS: All live births between 2012 and 2020 were screened for maternal diabetes and infant congenital heart defects using the French Medical Information System Program in Medicine, Surgery and Obstetrics database (PMSI-MCO). Incidences of these defects were estimated, and a logistic model evaluated maternal and fetal prognostic risk factors. RESULTS: Overall, 6,038,703 mothers did not have pre-gestational diabetes (no-diabetes), 23,147 had T1DM, and 14,401 had T2DM. The incidence of infant congenital disease was 6.2% for the no-diabetes group, 8.0%, for women with T1DM, and 8.4% for women with T2DM (P < 0.001); for congenital heart defects, incidences were respectively 0.8%, 3.0% and 2.7% (P < 0.001). In comparison with the no-diabetes group, the odds ratios (95%CI) of coronary heart defects were 2.07 (1.91;2.24) (P < 0.001) for women with T1DM and 2.20 (1.99;2.44) (P < 0.001) for women with T2DM, with no difference between T1DM and T2DM (P = 0.336). cesarian section, small and large for gestational age, and prematurity were also associated with an increased risk of congenital heart defects. CONCLUSION: In this study we observed higher incidences of congenital heart defects in infants of women with pre-gestational diabetes compared to women without pre-gestational diabetes, with no difference between women with T1DM or T2DM. These data call for intensifying preconception care and justify systematic cardiac echography in selected fetuses.

Impact of time to diagnosis on the occurrence of cardiogenic shock in MIS-C post-COVID-19 infection.

BACKGROUND: In multisystem inflammatory syndrome in children (MIS-C), diagnostic delay could be associated with severity. This study aims to measure the time to diagnosis in MIS-C, assess its impact on the occurrence of cardiogenic shock, and specify its determinants. METHODS: A single-center prospective cohort observational study was conducted between May 2020 and July 2022 at a tertiary care hospital. Children meeting the World Health Organization MIS-C criteria were included. A long time to diagnosis was defined as six days or more. Data on time to diagnosis were collected by two independent physicians. The primary outcome was the occurrence of cardiogenic shock. Logistic regression and receiver operating characteristic curve analysis were used for outcomes, and a Cox proportional hazards model was used for determinants. RESULTS: Totally 60 children were assessed for inclusion, and 31 were finally analyzed [52% males, median age 8.8 (5.7-10.7) years]. The median time to diagnosis was 5.3 (4.2-6.2) days. In univariable analysis, age above the median, time to diagnosis, high C-reactive protein, and high N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with cardiogenic shock [odds ratio (OR) 6.13 (1.02-36.9), 2.79 (1.15-6.74), 2.08 (1.05-4.12), and 1.70 (1.04-2.78), respectively]. In multivariable analysis, time to diagnosis ≥ 6 days was associated with cardiogenic shock [adjusted OR (aOR) 21.2 (1.98-227)]. Time to diagnosis ≥ 6 days had a sensitivity of 89% and a specificity of 77% in predicting cardiogenic shock; the addition of age > 8 years and NT-proBNP at diagnosis ≥ 11,254 ng/L increased the specificity to 91%. Independent determinants of short time to diagnosis were age < 8.8 years [aHR 0.34 (0.13-0.88)], short distance to tertiary care hospital [aHR 0.27 (0.08-0.92)], and the late period of the COVID-19 pandemic [aHR 2.48 (1.05-5.85)]. CONCLUSIONS: Time to diagnosis ≥ 6 days was independently associated with cardiogenic shock in MIS-C. Early diagnosis and treatment are crucial to avoid the use of inotropes and limit morbidity, especially in older children.

The Dietary Inflammatory Index Is Associated with Subclinical Mastitis in Lactating European Women.

Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: (1) test the association between the dietary inflammatory index (DII®) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.

Mode of Neonatal Delivery Influences the Nutrient Composition of Human Milk: Results From a Multicenter European Cohort of Lactating Women.

Background: The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months. Objective: This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life. Design: Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother's country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode. Results: Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation. Conclusion: Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life.

Risk factors for severe neonatal thrombocytopenia in cases of maternal immune thrombocytopenia.

AIM: Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not. METHODS: We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications. RESULTS: Severe nTP in the first 24 h after birth was more common in case of maternal splenectomy (OR = 4.4) and a previous severe nTP (OR = 46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR = 42), maternal treatment during pregnancy (OR = 2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications. CONCLUSION: In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery.

Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe.

PURPOSE: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. METHODS: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established. RESULTS: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. CONCLUSIONS: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study.

BACKGROUND: The effect on neonatal mortality of mode of delivery of a fetus in breech presentation at an extremely preterm gestational age remains controversial. OBJECTIVE: To compare mortality associated with planned vaginal delivery (PVD) of fetuses in breech presentation with that of fetuses in breech presentation with a planned cesarean delivery (PCD). MATERIAL AND METHODS: Retrospective study reviewing records over a 19-year period in a level 3 university referral center of singleton infants born between 25+0 and 27+6 weeks of gestation, alive on arrival in the delivery room, and weighing at least 500 grams at birth. Infants in the first group were in breech presentation with PVD and the second in breech presentation with PCD. The principal endpoint was neonatal death. RESULTS: During the study period, we observed 113 breech presentations with PVD, and 80 breech presentations with PCD. Although not significant after adjustment, neonatal mortality in the breech PVD group was more than twice that of the breech PCD group (19.5 vs 7.8%, P = 0.031, ORa = 2.6, 95% CI 0.8-9.3, NNT = 8). This higher neonatal mortality in the breech PVD group was exclusively associated with a higher risk of death in the delivery room (12.4 vs 0.0% P = 0.001, OR not calculable, NNT = 8). In these extremely preterm breech presentations with PVD, neonatal mortality in the delivery room was associated with entrapment of the aftercoming head, cord prolapse, and a short duration of labor. CONCLUSION: For deliveries between 25+0 and 27+6 weeks' gestation, vaginal delivery in breech presentation is associated with a higher risk of death in the delivery room.

Phototherapy Using a Light-Emitting Fabric (BUBOLight) Device in the Treatment of Newborn Jaundice: Protocol for an Interventional Feasibility and Safety Study.

BACKGROUND: Neonatal jaundice is a common condition occurring in 60%-80% of all healthy-term and late-preterm neonates. In the majority of cases, neonatal jaundice resolves spontaneously and causes no harm; however, in some neonates, significant hyperbilirubinemia can develop and lead to kernicterus jaundice, a serious neurological disease. Phototherapy (PT) is the preferred treatment for jaundice; however, to be effective, PT devices need to have a broad light emission surface to generate no or little heat and to provide an optimal wavelength and light intensity (420-490 nm and ≥30 µW/cm²/nm, respectively). OBJECTIVE: This study aimed to investigate the feasibility, safety, and level of satisfaction of parents and health care teams with the BUBOlight device, an innovative alternative to conventional hospital PT, in which luminous textiles have been incorporated in a sleeping bag. METHODS: This interventional, exploratory, simple group, nonrandomized, single-center trial will be conducted at Lille Hospital. In total, 10-15 neonates and their parents will be included to obtain evaluable data from 10 parent-neonate pairs. Neonates weighing more than 2500 g at birth and born with ≥37 weeks of amenorrhea that required PT in accordance with the guidelines of the National Institute For Health and Clinical Excellence will receive one 4-hour session of illumination. Total serum bilirubin and transcutaneous bilirubin levels were obtained at the start and 2 hours after the end of PT. Cutaneous and rectal temperatures, heart rate, and oxygen saturation will be measured at the beginning and during PT. The number of subjects is therefore not calculated on the basis of statistical assumptions. We aim to obtain a minimum proportion of 90% (ie, 9 of 10) of the neonates included, who have been able to undergo 4-hour PT without unacceptable and unexpected toxicities. We will calculate the mean, median, quartiles, minimum and maximum values of the quantitative parameters, and the frequency of the qualitative parameters. The rate of patients with no unacceptable and unexpected toxicities (ie, the primary endpoint) will be calculated. RESULTS: The first patient is expected to be enrolled at the end of 2020, and clinical investigations are intended for up to June 2021. The final results of this study are expected to be available at the end of 2021. CONCLUSIONS: Our findings will provide insights into the safety and feasibility of a new PT device based on light-emitting fabrics for the treatment of newborn jaundice. This new system, if proven effective, will improve the humanization of neonatal care and help avoid mother-child separation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04365998; https://clinicaltrials.gov/ct2/show/NCT04365998. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/24808.

Efficacy of Intact Cord Resuscitation Compared to Immediate Cord Clamping on Cardiorespiratory Adaptation at Birth in Infants with Isolated Congenital Diaphragmatic Hernia (CHIC).

Resuscitation at birth of infants with Congenital Diaphragmatic Hernia (CDH) remains highly challenging because of severe failure of cardiorespiratory adaptation at birth. Usually, the umbilical cord is clamped immediately after birth. Delaying cord clamping while the resuscitation maneuvers are started may: (1) facilitate blood transfer from placenta to baby to augment circulatory blood volume; (2) avoid loss of venous return and decrease in left ventricle filling caused by immediate cord clamping; (3) prevent initial hypoxemia because of sustained uteroplacental gas exchange after birth when the cord is intact. The aim of this trial is to evaluate the efficacy of intact cord resuscitation compared to immediate cord clamping on cardiorespiratory adaptation at birth in infants with isolated CDH. The Congenital Hernia Intact Cord (CHIC) trial is a prospective multicenter open-label randomized controlled trial in two balanced parallel groups. Participants are randomized either immediate cord clamping (the cord will be clamped within the first 15 s after birth) or to intact cord resuscitation group (umbilical cord will be kept intact during the first part of the resuscitation). The primary end-point is the number of infants with APGAR score <4 at 1 min or <7 at 5 min. One hundred eighty participants are expected for this trial. To our knowledge, CHIC is the first study randomized controlled trial evaluating intact cord resuscitation on newborn infant with congenital diaphragmatic hernia. Better cardiorespiratory adaptation is expected when the resuscitation maneuvers are started while the cord is still connected to the placenta.

Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation.

OBJECTIVE: Recent evidence indicates that levels of breast milk (BM) hormones such as leptin can fluctuate with maternal adiposity, suggesting that BM hormones may signal maternal metabolic and nutritional environments to offspring during postnatal development. The hormone apelin is highly abundant in BM but its regulation during lactation is completely unknown. Here, we evaluated whether maternal obesity and overnutrition impacted BM apelin and leptin levels in clinical cohorts and lactating rats. METHODS: BM and plasma samples were collected from normal-weight and obese breastfeeding women, and from lactating rats fed a control or a high fat (HF) diet during lactation. Apelin and leptin levels were assayed by ELISA. Mammary gland (MG) apelin expression and its cellular localization in lactating rats was measured by quantitative RT-PCR and immunofluorescence, respectively. RESULTS: BM apelin levels increased with maternal BMI, whereas plasma apelin levels decreased. BM apelin was also positively correlated with maternal insulin and C-peptide levels. In rats, maternal HF feeding exclusively during lactation was sufficient to increase BM apelin levels and decrease its plasma concentration without changing body weight. In contrast, BM leptin levels increased with maternal BMI in humans, but did not change with maternal HF feeding during lactation in rats. Apelin is highly expressed in the rat MG during lactation and was mainly localized to mammary myoepithelial cells. We found that MG apelin gene expression was up-regulated by maternal HF diet and positively correlated with BM apelin content and maternal insulinemia. CONCLUSIONS: Our study indicates that BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.

Human milk oligosaccharides, infant growth, and adiposity over the first 4 months of lactation.

BACKGROUND: The relationship between human milk oligosaccharides (HMOs) and infant growth and adiposity is not fully understood and comprehensive studies are missing from the current literature. METHODS: We screened and recruited 370 healthy, pregnant women and their infants from seven European countries. Breastmilk samples were collected using standardized procedures at six time points over 4 months, as were infant parameters. Correlations and associations between HMO area under the curve, anthropometric data, and fat mass at 4 months were tested. RESULTS: Lacto-N-neotetraose had a negative correlation with the change in length (rs = -0.18, P = 0.02). Sialyllacto-N-tetraose c (LSTc) had a positive correlation with weight for length (rs = 0.19, P = 0.015). Infants at the 25th upper percentile were fed milk higher in 3'-sialyllactose and LSTc (P = 0.017 and P = 0.006, respectively) compared to the lower 25th percentile of the weight-for-length z-score gain over 4 months of lactation. No significant associations between growth and body composition and Lewis or secretor-dependent HMOs like 2'-fucosyllactose were identified. CONCLUSIONS: Changes in the HMO composition of breastmilk during the first 4 months appear to have little influence on infant growth and body composition in this cohort of healthy mothers and infants. IMPACT: Modest associations exist between individual HMO and infant growth outcomes at least in healthy growing populations. Our study provides a comprehensive investigation of associations between all major HMO and infant growth and adiposity including several time points. Certain groups of HMOs, like the sialylated, may be associated with adiposity during the first months of lactation. HMO may modulate the risk of future metabolic disease. Future population studies need to address the role of specific groups of HMOs in the context of health and disease to understand the long-term impact.

Fermented infant formula (with Bifidobacterium breve C50 and Streptococcus thermophilus O65) with prebiotic oligosaccharides is safe and modulates the gut microbiota towards a microbiota closer to that of breastfed infants.

BACKGROUND & AIMS: Microbiome-modulators can help positively steer early-life microbiota development but their effects on microbiome functionality and associated safety and tolerance need to be demonstrated. We investigated the microbiome impact of a new combination of bioactive compounds, produced by the food-grade microorganisms Bifidobacterium breve C50 and Streptococcus thermophilus ST065 during a fermentation process, and prebiotics in an infant formula. Tolerance and safety were also assessed. METHODS: An exploratory prospective, randomized, double-blind, controlled, multi-centre study was designed to investigate the effect of bioactive compounds and prebiotics (short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS) 9:1). Experimental formulas containing these bioactive compounds and prebiotics (FERM/scGOS/lcFOS), prebiotics (scGOS/lcFOS), or bioactive compounds (FERM), were compared to a standard cow's milk-based control formula (Control). Exclusively breastfed infants were included as a reference arm since exclusive breastfeeding is considered as the optimal feeding for infants. The study lasted six months and included visits to health care professionals at baseline, two, four and six months of age. Stool SIgA concentration was the primary study outcome parameter. RESULTS: There were 280 infants randomized over the experimental arms and 70 infants entered the breastfed-reference arm. Demographics were balanced, growth and tolerance parameters were according to expectation and adverse events were limited. At four months of age the median SIgA concentration in the FERM/scGOS/lcFOS group was significantly higher compared to the Control group (p = 0.03) and was more similar to the concentrations found in the breastfed-reference group. Bifidobacterium increased over time in all groups. The FERM/scGOS/lcFOS combination resulted in a microbiota composition and metabolic activity closer to the breastfed infants' microbiome. CONCLUSION: The FERM/scGOS/lcFOS combination showed a significant positive effect on SIgA levels. All formulas tested were associated with normal growth and were well-tolerated. Additionally, at four months of age the FERM/scGOS/lcFOS formula brought the microbiome composition and metabolic activity closer towards that of breastfed infants. CLINICAL TRIAL REGISTRY: Registration number NTR2726 (Netherlands Trial Register; www.trialregister.nl/).

Screening for neurodevelopmental disorders in children with congenital heart disease.

The aim of this study was to evaluate the frequency of neurodevelopmental disorders (NDD) in children with significant congenital heart disease (CHD) and to determine associated factors to NDD and frequency of follow-up in developmental therapies. Two hundred and ten children with significant CHD aged from 6 to 66 months were enrolled over a period of six months. The Ages & Stages Questionnaire Third Edition in French (ASQ-3) was used to assess neurodevelopmental domains. NDD were defined if cut-off scores were ≤ - 1SD. - 1SD corresponded to "Monitor" range: children with minor or emerging disorders; - 2SD corresponded to "Refer" range: children exhibiting neurodevelopmental delays. Forty children were in "Monitor" range and 86 in "Refer" range. NDD rate was 60.0% (n = 126, 95% CI, 53.4 to 66.6%). There was no difference regarding CHD severity (p = 0.99). Only the presence of non-cardiac disease (OR = 2.14; 95% CI, 1.11 to 4.20) was associated with NDD. Forty-six children with NDD had no developmental follow-up (among them 21 were in "Refer" range (10%)) despite this being available.Conclusion: Children with significant CHD are at risk for NDD regardless of CHD severity. Systematic and early monitoring in a specific care program is required. Barriers that prevent access of care must be identified.Trial registration: Neurodevelopmental Disorders in Children With Congenital Heart Disease. NeuroDis-CHD. NCT03360370. https://clinicaltrials.gov/ct2/show/NCT03360370 What is Known: • Children with CHD are at risk for neurodevelopmental disorders and behavioural problems impacting their social adaptation, academic achievements and quality of personal and family life even in adulthood. What is New: • Children with CHD are at risk for neurodevelopmental disorders regardless of the complexity of the CHD. • Even with the availability of appropriate developmental services, children with CHD are not correctly followed, highlighting the need of a specific program of care for a better outcome. Local barriers that prevent access of care of those children must be identified.

Umbilical cord arterial and venous gases, ionogram, and glucose level for predicting neonatal morbidity at term.

OBJECTIVE: To determine which parameter of umbilical arterial cord gas analysis, pH, base deficit, lactate concentration, ionogram values, or glucose level index is the best predictor of neonatal morbidity at term. DESIGN: We conducted a 15-month retrospective cohort study that included all nonanomalous, singleton, term births at a single center. The predictive ability of lactate concentration, base deficit, pH, ionogram values, and glucose level were compared using receiver-operating characteristic curves for global and neurological composite morbidity. Optimal cutoff values for lactate concentration, base deficit, and pH were estimated based on their maximum area under the curve. RESULTS: We included 5161 newborns: 52 (1.01 %) had global composite morbidity, and 17 had (0.33 %) neurological composite morbidity. Blood levels of potassium, calcium, natremia, glucose level, and HCO3- did not differ significantly between groups. pH, partial pressure of CO2, partial pressure of O2, base deficit, and lactate levels differed significantly between neonates in the groups with and without global composite morbidity. Nearly similar results were found for neurological composite morbidity. The predictive ability did not differ between arterial pH and arterial lactate concentration (P = .25) and base deficit (P = .79). Optimal cutoff values to predict global composite morbidity were arterial pH 7.144, venous pH 7.236, and arterial lactate concentration 6.5 mmol/L. CONCLUSIONS: Acid-base status analysis remains the best objective indicator for predicting neonatal morbidity and can be estimated using pH, lactate, or base deficit. Ionogram cord blood composition and glucose level do not appear to be useful for this purpose.

Prostaglandin E1 in infants with congenital diaphragmatic hernia (CDH) and life-threatening pulmonary hypertension.

BACKGROUND: Suprasystemic pulmonary hypertension (PH) is highly predictive of pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of Prostaglandin E1 (PGE1) in newborns with severe CDH and life-threatening PH. METHODS: Newborn infants with isolated CDH and life-threatening PH defined by an acute worsening of the cardiorespiratory function, and bidirectional or exclusive right-to-left shunting across the ductus arteriosus (DA) with an acceleration of the blood flow >1.5 m.s-1 assessed by Doppler echocardiography. Serial measurements of cardiorespiratory variables have been recorded before and after PGE1. RESULTS: 18 infants (out of 102 in the cohort) were included in the study (gestational age: 39 ±â€¯2 weeks). The median FiO2, and preductal and postductal SpO2 were 80% [50; 100], 91% [88; 95] and 86% [82; 91], respectively, before treatment. FiO2 decreased to 35% [30-40] (p = 0.001) at H6. Maximal blood flow velocities in the DA decreased after starting PGE1 from 2.2 m.s-1 [1.5-2.5] to 1 m.s-1 [0.55-1.2] (p < 0.001). CONCLUSIONS: PGE1 treatment improved oxygenation and circulatory function in newborn infants with severe CDH and life-threatening PH. Our data provide evidence that restrictive DA may result in suprasystemic pulmonary hypertension in CDH infants, and that PGE1 may improve cardiorespiratory failure through reopening of the DA. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.