Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Association Between Assisted Reproductive Technology and Cerebral Palsy: A Meta-Analysis.

BACKGROUND: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years. METHODS: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses. RESULTS: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63). CONCLUSIONS: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk.

Time of leaving work pregnancy results during COVID-19 pandemic. The MOACC-19 cohort from Spain.

BACKGROUND: COVID-19 pandemic has changed the way pregnancies have been controlled as well as working conditions. In countries with paid leave of work, leaving earlier has been a relevant measure for controlling the pandemic. No study has been published on factors associated with earlier leaving work in pregnancy and the consequences it could have on pregnancy outcomes. OBJECTIVE: We aimed to identify woman and pregnancy characteristics associated with leaving work earlier and its consequences on pregnancy results. METHOD: A cohort study was carried out in Cantabria, Northern Spain, including 760 women who were pregnant in 2020 and were working at the beginning of their pregnancy. Data on pregnancy characteristics and results were obtained from medical records and gestational age at leaving work was self-reported. In a logistic regression analysis, leaving work before 26th week of pregnancy was the main effect variable. RESULTS: Several factors were associated with lower probability of leaving work before 26th week, including university studies (OR = 0.49, 95% CI: 0.36, 0.68), having presential work (OR = 0.57, 95% CI: 0.40, 0.81), women born in non-European countries (OR = 0.55, 95% CI: 0.30, 1.01) and non-smokers (OR for smokers = 1.79, 95% CI: 1.12, 2.87). Neither type of delivery, gestational age at delivery nor other pregnancy results were associated with the gestational age of leaving work. CONCLUSION: Several pregnancy and women characteristics were associated with leaving work earlier in the COVID-19 pandemic, although it was not associated with any pregnancy outcome.

Feeding in the first six months of life is associated with the probability of having bronchiolitis: a cohort study in Spain.

BACKGROUND: Breastfeeding is associated with lower incidence and severity of lower respiratory tract disease. However, little is known about the relationship between feeding type and breastfeeding duration with bronchiolitis in a child's first year. METHODS: A prospective cohort study of 969 newborn babies were followed-up for 12 months to determine breastfeeding duration, feeding type, feeding trajectory, and bronchiolitis episodes at Marqués de Valdecilla University Hospital, Spain in 2018. Type of feeding was recorded by interviewing mothers at the time of hospital discharge and at 2, 4, 6, 9 and 12 months of life, in three categories: breastfeeding, mixed feeding and infant formula. Type of feeding at hospital discharge refers to feeding from birth to discharge. In any other times studied, it refers to feeding in the last 24 h. The association between the feeding type and bronchiolitis was analysed using logistic regression. Poisson regression was used to evaluate the association between feeding type and the number of bronchiolitis episodes with Kaplan-Meier estimators presenting the cumulative probability of suffering bronchiolitis. The results were adjusted for mother and child characteristics. RESULTS: Our data shows exclusive breastfeeding and mixed breastfeeding reduce the number of episodes of bronchiolitis. Regarding feeding at 4 months, exclusive breastfeeding reduced by 41% the number of episodes of bronchiolitis (adjusted incidence Ratio (aIR) 0.59, 95% CI 0.46, 0.76) and mixed feeding by 37% (aIR 0.63, 95% CI 0.47, 0.86). Moreover, changing from exclusive breastfeeding to mixed feeding increased the incidence of bronchiolitis compared with continuing exclusive breastfeeding. An early swap to mixed breastfeeding before months 2 or 4, was associated with a reduced the number of episodes of bronchiolitis, (aIR 0.53, 95% CI 0.39, 0.73 if introduction of mixed breastfeeding before month 2, and aIR 0.61, 95% CI 0.45, 0.83 if introduction of mixed breastfeeding before month 4), when compared with infant formula alone. CONCLUSIONS: Any breastfeeding was associated with lower incidence of bronchiolitis and number of episodes of bronchiolitis in the first year of life. Consequently, promoting programmes facilitating exclusive or mixed breastfeeding would be a relevant measure in the prevention of bronchiolitis.

Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort.

The new coronavirus, SARS-CoV-2, is devastating for specific groups of patients, but currently there is not enough information concerning its effects on pregnant women. The purpose of this study is to identify the impact of SARS-CoV-2 infection on pregnancy and the consequences that it could cause. We studied a cohort of pregnant ladies who were tested for SARS-CoV-2 infection by RT-PCR and classified as infected or not infected. The recruitment was carried out in the HUMV hospital, a third-level hospital located in Santander, northern Spain. It started on 23 March 2020 and ended on 14 October 2020. Data from our cohort were compared to another cohort recruited in 2018 at the same hospital. We found that gestational hypertension, placental abruptio, and home exposure to an infected person, among other variables, could be associated with SARS-CoV-2 infection. In conclusion, we consider pregnant women a high-risk group of patients towards a possible SARS-CoV-2 infection, especially those who present with conditions such as gestational hypertension or obesity; moreover, we think that SARS-CoV-2 infection could increase the possibilities of having an abruptio placentae, although this result was found in only a few women, so it requires further confirmation.

Influence of Socioeconomic Status on SARS-CoV-2 Infection in Spanish Pregnant Women. The MOACC-19 Cohort.

Little is known on socio-economic factors associated with SARS-CoV-2 infection in pregnant women. Here, we analyze the relationship between educational, occupational, and housing variables with SARS-CoV-2 infection in a cohort of 988 pregnant women in Spain. Pregnant women were recruited at the University Hospital Marques de Valdecilla, Santander, Spain, among those delivering from 23 March 2020 onwards or consulting for their 12th week of pregnancy from 26 May 2020 onwards. Information on occupational variables and housing characteristics was self-reported. Pregnant women were tested for a current or past infection of SARS-CoV-2 using both PCR and antibodies detection (ELISA). Logistic regression models were used to analyze factors associated with SARS-CoV-2 infection, adjusting for age and country of origin. Infection by SARS-CoV-2 was not associated with educational level or occupational variables, except for where the pregnant woman was a healthcare worker (odds ratio (OR) = 2.87, 95% confidence interval (CI): 0.84-9.79). Housing with four or more rooms (OR = 2.07, 95% CI: 0.96-4.47), four or more people in the household (OR = 1.91, 95% CI: 0.89-4.14), lack of heating (OR = 2.81, 95% CI: 1.24-6.34) and less than 23 square meters per person (OR = 3.97, 95% CI: 1.43-11.1) were the housing characteristics associated with SARS-CoV-2 infection. Housing characteristics, but not occupational or educational variables, were associated with SARS-CoV-2 infection. Guidelines on the prevention of COVID-19 should reinforce household measures to prevent pregnant women from becoming infected by their relatives.

Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity.

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis.

Factors associated with duration of breastfeeding in Spain: a cohort study.

BACKGROUND: Factors associated with duration of breastfeeding have been usually studied at specific times after birth. Little is known about how much time is added to breastfeeding by each associated factor. METHODS: A cohort of 969 mother-child dyads was followed-up for twelve months at the Marqués de Valdecilla University Hospital, Spain, in 2018. Data on mother characteristics, pregnancy, delivery and children characteristics were obtained from medical records. Length of breastfeeding was reported by the mothers and recorded in paediatric medical record at hospital discharge and 2, 4, 6, 9 and 12 months of life. Factors associated with duration of breastfeeding were analysed via multivariate Weibull regression parameterized as accelerated time of failure. Results are presented as time ratios. RESULTS: About four out of five children were breastfed at hospital discharge, although this proportion dropped to 65% in children born from smoker women, 70% in preterm children and 68% in neonates weighting less than 2500 g. Mother's age was associated with longer breastfeeding, adding 2% more breastfeeding time per year (adjusted time ratio 1.02; 95% confidence interval 1.00, 1.04). Children born from mothers with university studies were breastfed 53% more time than those born from mothers with primary studies (adjusted time ratio 1.53; 95% confidence interval 1.21, 1.95); smoking in pregnancy decreased length of breastfeeding by 41% (adjusted time ratio 0.59; 95% confidence interval 0.46, 0.76). Other factors associated with longer breastfeeding were single pregnancy and newborn weight over 2500 g. CONCLUSIONS: Analysing factors associated with duration of breastfeeding as time parameters allows us to quantify the amount of time gained or lost by each factor, which could make it easier to evaluate the relevance of programmes directed to promote facilitating breastfeeding factors.

Health Care Costs Associated to Type of Feeding in the First Year of Life.

BACKGROUND: Breastfeeding is associated with lower risk of infectious diseases, leading to fewer hospital admissions and pediatrician consultations. It is cost saving for the health care system, however, it is not usually estimated from actual cohorts but via simulation studies. METHODS: A cohort of 970 children was followed-up for twelve months. Data on mother characteristics, pregnancy, delivery and neonate characteristics were obtained from medical records. The type of neonate feeding at discharge, 2, 4, 6, 9 and 12 months of life was reported by the mothers. Infectious diseases diagnosed in the first year of life, hospital admissions, primary care and emergency room consultations and drug treatments were obtained from neonate medical records. Health care costs were attributed using public prices and All Patients Refined-Diagnosis Related Groups (APR-DRG) classification. RESULTS: Health care costs in the first year of life were higher in children artificially fed than in those breastfed (1339.5€, 95% confidence interval (CI): 903.0-1775.0 for artificially fed vs. 443.5€, 95% CI: 193.7-694.0 for breastfed). The breakdown of costs also shows differences in primary care consultations (295.7€ for formula fed children vs. 197.9€ for breastfed children), emergency room consultations (260.1€ for artificially fed children vs. 196.2€ for breastfed children) and hospital admissions (791.6€ for artificially fed children vs. 86.9€ for breastfed children). CONCLUSIONS: Children artificially fed brought about more health care costs related to infectious diseases than those exclusively breastfed or mixed breastfed. Excess costs were caused in hospital admissions, primary care consultations, emergency room consultations and drug consumption.

Meningitis neumocócica en Cantabria (España) en la era de las vacunas conjugadas antineumocócicas (2001-2015) / Pneumococcal meningitis in Cantabria (Spain) in the pneumococcal conjugate vaccine era (2001-2015)

Objetivo. Analizar las características de la meningitis neumocócica en < 14 años tras la comercialización de vacunas antineumocócicas conjugadas en nuestra comunidad. Métodos. Estudio retrospectivo de los casos de meningitis neumocócica en el que se analizaron dos períodos: pre vacuna antineumocócica trecevalente (VNC13v) (2001-2010) y post-VNC13v (2010-2015). Se recogieron datos demográficos y clínicos de los pacientes y datos microbiológicos. Resultados. Se diagnosticaron 18 casos. La incidencia media pre-VNC13v fue de 2,3/100 000, y disminuyó a 0,5/100 000 tras la VNC13v. Los serotipos más frecuentemente identificados fueron 6A y 10A (pre-VNC13v); 6B y 15B (post-VNC13v, solo dos casos). Trece de dieciocho pacientes ingresaron en la Unidad de Cuidados Intensivos. Todos los casos fueron tratados con cefotaxima y recibieron dexametasona 14/18. Seis pacientes sobrevivieron con secuelas y uno falleció. Conclusión. Se observa un importante descenso en la incidencia de meningitis neumocócica desde la comercialización de la VNC13v, por lo que cabe esperar que tras su introducción sistemática se produzca un descenso aún mayor.

Objective. To analyze the characteristics of pneumococcal meningitis in children < 14 years old following the market introduction of pneumococcal conjugate vaccines in our community. Methods. Retrospective study of pneumococcal meningitis cases with a two-period analysis: pre-13-valent pneumococcal conjugate vaccine (PCV13) (2001-2010) and post-PCV13 (2010-2015). Patient demographic and clinical data, and microbiological data were collected. Results. Eighteen cases were diagnosed. The mean incidence in the pre-PCV13 period was 2.3/100 000, which reduced to 0.5/100 000 after the PCV13 introduction. The most commonly identified serotypes were 6A and 10A (pre-PCV13); 6B and 15B (post-PCV13, only 2 cases). Out of 18 patients, 13 were admitted to the intensive care unit. All cases were treated with cefotaxime, and 14/18 received dexamethasone. Six patients survived with sequelae, and 1 died. Conclusion. A major reduction has been observed in the incidence of pneumococcal meningitis since the introduction of the PCV13 to the market, so an even greater reduction is expected following its systematic introduction.

Pneumococcal meningitis in Cantabria (Spain) in the pneumococcal conjugate vaccine era (2001-2015). / Meningitis neumocócica en Cantabria (España) en la era de las vacunas conjugadas antineumocócicas (2001-2015).

OBJECTIVE: To analyze the characteristics of pneumococcal meningitis in children ≤ 14 years old following the market introduction of pneumococcal conjugate vaccines in our community. METHODS: Retrospective study of pneumococcal meningitis cases with a two-period analysis: pre-13-valent pneumococcal conjugate vaccine (PCV13) (2001-2010) and post-PCV13 (2010-2015). Patient demographic and clinical data, and microbiological data were collected. RESULTS: Eighteen cases were diagnosed. The mean incidence in the pre-PCV13 period was 2.3/100 000, which reduced to 0.5/100 000 after the PCV13 introduction. The most commonly identified serotypes were 6A and 10A (pre-PCV13); 6B and 15B (post-PCV13, only 2 cases). Out of 18 patients, 13 were admitted to the intensive care unit. All cases were treated with cefotaxime, and 14/18 received dexamethasone. Six patients survived with sequelae, and 1 died. CONCLUSION: A major reduction has been observed in the incidence of pneumococcal meningitis since the introduction of the PCV13 to the market, so an even greater reduction is expected following its systematic introduction.

Analizar las características de la meningitis neumocócica en ≤ 14 años tras la comercialización de vacunas antineumocócicas conjugadas en nuestra comunidad.