ResearchPad - neonates https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Newborn body composition after maternal bariatric surgery]]> https://www.researchpad.co/article/elastic_article_13862 In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB.Material and methodsMother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013.ResultsWe included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery.ConclusionOffspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth. ]]> <![CDATA[Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth]]> https://www.researchpad.co/article/elastic_article_13878 Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study’s objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41–63%), 82% negative predictive value (NPV, 95% CI 73–88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81–95%), 81% NPV (95% CI 77–85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81–95%) with superior NPV (87%, 95% CI 84–90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

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<![CDATA[Managing possible serious bacterial infection of young infants where referral is not possible: Lessons from the early implementation experience in Kushtia District learning laboratory, Bangladesh]]> https://www.researchpad.co/article/elastic_article_7649 Serious infections account for 25% of global newborn deaths annually, most in low-resource settings where hospital-based treatment is not accessible or feasible. In Bangladesh, one-third of neonatal deaths are attributable to serious infection; in 2014, the government adopted new policy for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral was not possible. We conducted implementation research to understand what it takes for a district health team to implement quality outpatient PSBI management per national guidelines.MethodsPSBI management was introduced as part of the Comprehensive Newborn Care Package in 2015. The study piloted this package through government health systems with limited partner support to inform scale-up efforts. Data collection included facility register reviews for cases seen at primary level facilities; facility readiness and provider knowledge and skills assessments; household surveys capturing caregiver knowledge of newborn danger signs and care-seeking for newborn illness; and follow-up case tracking, capturing treatment adherence and outcomes. Analysis consisted of descriptive statistics.ResultsOver the 15-month implementation period, 1432 young infants received care, of which 649 (45%) were classified as PSBI. Estimated coverage of care-seeking increased from 22% to 42% during the implementation period. Although facility readiness and providers’ skills increased, providers’ adherence to guidelines was not optimal. Among locally managed PSBI cases, 75% completed the oral antibiotic course and 15% received the fourth day follow-up. Care-seeking remained high among private providers (95%), predominantly village health doctors (over 80%).ConclusionsFacility readiness, including health care provider knowledge and skills were strengthened; future efforts should focus on improving provider adherence to guidelines. Social and behavior change strategies targeting families and communities should explore shifting care-seeking from private, possibly less-qualified providers. Strategies to improve private sector management of PSBI cases and improved linkages between private and public sector providers could be explored. ]]> <![CDATA[Neonatal sepsis in Iran: A systematic review and meta-analysis on national prevalence and causative pathogens]]> https://www.researchpad.co/article/Nc80eb6d8-6c1e-4acb-a5fa-a329abafdd28

Background

Neonatal sepsis is accounted for 30–50% of annual neonatal deaths in developing countries. We performed a systematic review and meta-analysis study to evaluate the national prevalence and identification of the etiological pathogens of neonatal sepsis in Iran.

Methods

A comprehensive literature search was done on the national and international databases for studies published between 2000 and 2019. The DerSimonian and Laird random-effects model was used to calculate pooled prevalence estimates, with 95% confidence intervals (CIs). Subgroup analyses and meta-regressions regarding the gender, type of sepsis and time during were also performed. Data were extracted, analyzed, and presented according to PRISMA guideline.

Results

Of 944 publications identified, 22 studies containing 14,683 neonates met the eligibility criteria. The pooled national prevalence of sepsis in Iran was 15.98% (95%CI, 11.96–20.46%; 1,367/14,683). Prevalence rate in boys (20.42%; 95%CI, 9.03–34.8%) was slightly higher than girls (18.5%; 95%CI, 7.4–32.8). A decreasing trend in prevalence of neonatal sepsis was found in recent years, although not statistically significant (c = -0.005; P value = 0.4). The most prevalent causative bacterial pathogens were Enterobacter spp. (23.04%), followed by Klebsiella pneumoniae (17.54%), coagulase-negative Staphylococci (14.06%), Escherichia coli (13.92%), Pseudomonas aeruginosa (12.67%), and Staphylococcus aureus (11.48%).

Conclusion

Our findings showed a high prevalence of neonatal sepsis in suspected neonates, suggesting the need to implement preventive measures, routine assessment, and close monitoring of neonates. Also, Enterobacter spp. and Klebsiella pneumoniae were identified as the principal bacterial pathogens responsible for neonatal septicemia in Iran.

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<![CDATA[Candida lusitaniae in Kuwait: Prevalence, antifungal susceptibility and role in neonatal fungemia]]> https://www.researchpad.co/article/5c8accced5eed0c484990063

Objectives

Candida lusitaniae is an opportunistic yeast pathogen in certain high-risk patient populations/cohorts. The species exhibits an unusual antifungal susceptibility profile with tendency to acquire rapid resistance. Here, we describe prevalence of C. lusitaniae in clinical specimens in Kuwait, its antifungal susceptibility profile and role in neonatal fungemia.

Methods

Clinical C. lusitaniae isolates recovered from diverse specimens during 2011 to 2017 were retrospectively analyzed. All isolates were identified by germ tube test, growth on CHROMagar Candida and by Vitek 2 yeast identification system. A simple species-specific PCR assay was developed and results were confirmed by PCR-sequencing of ITS region of rDNA. Antifungal susceptibility was determined by Etest. Minimum inhibitory concentrations (MICs) were recorded after 24 h incubation at 35°C.

Results

Of 7068 yeast isolates, 134 (1.89%) were identified as C. lusitaniae including 25 (2.52%) among 990 bloodstream isolates. Species-specific PCR and PCR-sequencing of rDNA confirmed identification. Of 11 cases of neonatal candidemia, 9 occurred in NICU of Hospital A and are described here. Eight of 9 neonates received liposomal amphotericin B, which was followed by fluconazole in 7 and additionally by caspofungin in 2 cases as salvage therapy. Three of 8 (37.5%) patients died. No isolate exhibited reduced susceptibility to amphotericin B, fluconazole, voriconazole, caspopfungin, micafungin and anidulafungin. The MIC ± geometric mean values for amphotericin B, fluconazole, voriconazole, and caspofungin were as follows: 0.072 ± 0.037 μg/ml, 2.32 ± 0.49 μg/ml, 0.09 ± 0.01 μg/ml and 0.16 ± 0.08 μg/ml, respectively. Only two isolates exhibited reduced susceptibility to fluconazole.

Conclusions

This study describes the prevalence and antifungal susceptibility profile of clinical C. lusitaniae isolates in Kuwait. No isolate showed reduced susceptibility to amphotericin B. The study highlights the emerging role of C. lusitaniae as a healthcare-associated pathogen capable of causing fungemia in preterm neonates and causing significant mortality.

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<![CDATA[A prospective, multi-center study of Candida bloodstream infections in Chile]]> https://www.researchpad.co/article/5c8c1960d5eed0c484b4d4f3

Background

Active surveillance is necessary for improving the management and outcome of patients with candidemia. The aim of this study was to describe epidemiologic and clinical features of candidemia in children and adults in tertiary level hospitals in Chile.

Methods

We conducted a prospective, multicenter, laboratory-based survey study of candidemia in 26 tertiary care hospitals in Chile, from January 2013 to October 2017.

Results

A total of 780 episodes of candidemia were included, with a median incidence of 0.47/1,000 admissions. Demographic, clinical and microbiological information of 384 cases of candidemia, from 18 hospitals (7,416 beds), was included in this report. One hundred and thirty-four episodes (35%) occurred in pediatric patients and 250 (65%) in adult population. Candida albicans (39%), Candida parapsilosis (30%) and Candida glabrata (10%) were the leading species, with a significant difference in the distribution of species between ages. The use of central venous catheter and antibiotics were the most frequent risk factors in all age groups (> 70%). Three hundred and fifteen strains were studied for antifungal susceptibility; 21 strains (6.6%) were resistant to fluconazole, itraconazole, voriconazole, anidulafungin or micafungin. The most commonly used antifungal therapies were fluconazole (39%) and echinocandins (36%). The overall 30-day survival was 74.2%, significantly higher in infants (82%) and children (86%) compared with neonates (72%), adults (71%) and elderly (70%).

Conclusions

Our prospective, multicenter surveillance study showed a low incidence of candidemia in Chile, with high 30-day survival, a large proportion of elderly patients, C. glabrata as the third most commonly identified strain, a 6.6% resistance to antifungal agents and a frequent use of echinocandins.

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<![CDATA[Implementing the INTERGROWTH-21st gestational dating and fetal and newborn growth standards in peri-urban Nairobi, Kenya: Provider experiences, uptake and clinical decision-making]]> https://www.researchpad.co/article/5c8c1980d5eed0c484b4d7dd

Background

Perinatal and newborn complications are major risk factors for unfavorable fetal and neonatal outcomes. Gestational dating and growth monitoring can be instrumental in the identification and management of high-risk pregnancies and births. The INTERGROWTH-21st Project developed the first global standards for gestational dating and fetal and newborn growth monitoring, supplying a toolkit for clinicians. This study aimed to assess the feasibility and acceptability of the first known implementation study of these standards in a low resource setting.

Methods

The study was performed in two 12-month phases from March 2016 to March 2018 at Jacaranda Health, a private maternity hospital in peri-urban Nairobi, Kenya. In-depth interviews, focus group discussions and a provider survey were utilized to evaluate providers’ experiences during implementation. Client chart data, for pregnant women attending antenatal care and/or delivering at Jacaranda Health along with their newborns, were captured to assess uptake and effect of the standards on clinical decision-making.

Results

Facility-level support and provider buy-in proved to be critical factors driving the success of implementing the standards. However, additional support was needed to strengthen capacity to conduct and interpret ultrasounds and maintain motivation among providers. We observed a significant increase in the uptake of obstetric ultrasounds, particularly gestational dating, during the implementation of the standards. Although no significant changes were detected in the identification of high-risk pregnancies, referrals and deliveries by Cesarean section during implementation, we did observe a significant reduction in inductions for post-date. No significant barriers were reported regarding the use of the newborn standards. Over 80% of providers advocated for the standards to remain in place with some enhancements related mainly to training, advocacy and procurement.

Conclusions

The findings are timely with increasing global adoption of the standards and the challenging and multi-faceted nature of translating new, evidence-based guidelines into routine clinical practice.

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<![CDATA[Arterial carboxyhaemoglobin levels in children admitted to PICU: A retrospective observational study]]> https://www.researchpad.co/article/5c8accf2d5eed0c4849903c7

While carbon monoxide (CO) is considered toxic, low levels of endogenously produced CO are protective against cellular injury induced by oxidative stress. Carboxyhaemoglobin (COHb) levels have been associated with outcomes in critically ill adults. We aimed to describe the distribution of carboxyhaemoglobin in critically ill children and the relationship of these levels with clinical outcomes. This retrospective observational study was conducted at a large tertiary paediatric intensive care unit (PICU). We included all children admitted to the PICU over a two-year period who underwent arterial blood gas analysis. We measured the following: (i) Population and age-related differences in COHb distribution; (ii) Change in COHb over the first week of admission using a multi-level linear regression analysis; (iii) Uni- and multivariable relationships between COHb and length of ventilation and PICU survival. Arterial COHb levels were available for 559/2029 admissions. The median COHb level was 1.20% (IQR 1.00–1.60%). Younger children had significantly higher COHb levels (p-value <2 x 10−16). Maximum Carboxyhaemoglobin was associated with survival 1.67 (95% CI: 1.01–2.57; p-value = 0.02) and length of ventilation (OR 5.20, 95% CI: 3.07–7.30; p-value = 1.8 x 10−6) following multi-variable analysis. First measured and minimum COHb values were weakly associated with length of ventilation, but not survival. In conclusion, children have increased COHb levels in critical illness, which are greater in younger children. Higher COHb levels are associated with longer length of ventilation and death in PICU. This may reflect increased oxidative stress in these children.

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<![CDATA[The Bos taurus maternal microbiome: Role in determining the progeny early-life upper respiratory tract microbiome and health]]> https://www.researchpad.co/article/5c89770cd5eed0c4847d233e

Natural transference of maternal microbes to the neonate, especially at birth via the vaginal canal, has recently been recognized in humans and cows; however, its microbial influence on calf health has not yet been documented. We compared the bacterial communities in vaginal and fecal samples from 81 pregnant dairy cows versus those in nasopharyngeal and fecal samples collected at 3, 14 and 35 days of life from their respective progeny. The microbiota of the calf upper respiratory tract (URT), regardless of calf age, was found to be highly similar to the maternal vaginal microbiota. Calf fecal microbiota clustered closely to the maternal fecal microbiota, progressing toward an adult-like state over the first 35 days when relative abundances of taxa were considered. Sixty-four, 65 and 87% of the detected OTUs were shared between cow and calf fecal microbiota at days 3, 14 and 35 respectively, whereas 73, 76 and 87% were shared between maternal vaginal microbiome and calf URT microbiota at days 3, 14 and 35, respectively. Bacteroidetes, Ruminococcus, Clostridium, and Blautia were the top four genera identified in maternal and calf fecal samples. Mannheimia, Moraxella, Bacteroides, Streptococcus and Pseudomonas were the top five genera identified in maternal vaginal and calf URT samples. Mannheimia was relatively more abundant in the vaginal microbiota of cows whose progeny were diagnosed with respiratory and middle ear disease. Our results indicate that maternal vaginal microbiota potentially influences the initial bacterial colonization of the calf URT, and that might have an important impact on the health of the calf respiratory tract and middle ear.

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<![CDATA[Exploring clinical, echocardiographic and molecular biomarkers to predict bronchopulmonary dysplasia]]> https://www.researchpad.co/article/5c89778ad5eed0c4847d2f5c

Introduction

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in childhood, related to prematurity, and the most common cause of pulmonary hypertension (PH) secondary to pulmonary disease in children. Moderate and severe BPD have a worse outcome and relate more frequently with PH. The prediction of moderate or severe BPD development in extremely premature newborns is vital to implement preventive strategies. Starting with the hypothesis that molecular biomarkers were better than clinical and echocardiographic factors, this study aims to explore the ability of clinical, echocardiographic and analytical variables to predict moderate or severe BPD in a cohort of extremely preterm infants.

Patients and methods

We designed a prospective longitudinal study, in which we followed a cohort of preterm newborns (gestational age <28 weeks and weight ≤ 1250 grams). In these newborns we recorded weekly clinical and echocardiographic variables as well as blood and tracheal aspirate samples, to analyze molecular biomarkers (IL-6, IL-1, IP10, uric acid, HGF, endothelin-1, VEGF, CCL5). Variables and samples were collected since birth up to week 36 (postmenstrual age), time-point at which the diagnosis of BPD is established.

Results

We included 50 patients with a median gestational age of 26 weeks (IQR 25–27) and weight of 871 g (SD 161,0) (range 590-1200g). Three patients were excluded due to an early death. Thirty-five patients (74.5%) developed BPD (mild n = 14, moderate n = 15, severe n = 6). We performed a logistic regression in order to identify risk factors for moderate or severe BPD. We compared two predictive models, one with two variables (mechanical ventilation and inter-ventricular septum flattening), and another-one with an additional molecular biomarker (ET-1).

Conclusions

The combination of clinical and echocardiographic variables is a valuable tool for determining the risk of BPD. We find the two variable model (mechanical ventilation and echocardiographic signs of PH) more practical for clinical and research purposes. Future research on BPD prediction should be oriented to explore the potential role of ET-1.

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<![CDATA[Dual role of DMXL2 in olfactory information transmission and the first wave of spermatogenesis]]> https://www.researchpad.co/article/5c6730a1d5eed0c484f37e0e

Gonad differentiation is a crucial step conditioning the future fertility of individuals and most of the master genes involved in this process have been investigated in detail. However, transcriptomic analyses of developing gonads from different animal models have revealed that hundreds of genes present sexually dimorphic expression patterns. DMXL2 was one of these genes and its function in mammalian gonads was unknown. We therefore investigated the phenotypes of total and gonad-specific Dmxl2 knockout mouse lines. The total loss-of-function of Dmxl2 was lethal in neonates, with death occurring within 12 hours of birth. Dmxl2-knockout neonates were weak and did not feed. They also presented defects of olfactory information transmission and severe hypoglycemia, suggesting that their premature death might be due to global neuronal and/or metabolic deficiencies. Dmxl2 expression in the gonads increased after birth, during follicle formation in females and spermatogenesis in males. DMXL2 was detected in both the supporting and germinal cells of both sexes. As Dmxl2 loss-of-function was lethal, only limited investigations of the gonads of Dmxl2 KO pups were possible. They revealed no major defects at birth. The gonadal function of Dmxl2 was then assessed by conditional deletions of the gene in gonadal supporting cells, germinal cells, or both. Conditional Dmxl2 ablation in the gonads did not impair fertility in males or females. By contrast, male mice with Dmxl2 deletions, either throughout the testes or exclusively in germ cells, presented a subtle testicular phenotype during the first wave of spermatogenesis that was clearly detectable at puberty. Indeed, Dmxl2 loss-of-function throughout the testes or in germ cells only, led to sperm counts more than 60% lower than normal and defective seminiferous tubule architecture. Transcriptomic and immunohistochemichal analyses on these abnormal testes revealed a deregulation of Sertoli cell phagocytic activity related to germ cell apoptosis augmentation. In conclusion, we show that Dmxl2 exerts its principal function in the testes at the onset of puberty, although its absence does not compromise male fertility in mice.

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<![CDATA[Investigating pathways linking women’s status and empowerment to skilled attendance at birth in Tanzania: A structural equation modeling approach]]> https://www.researchpad.co/article/5c6dc9cbd5eed0c48452a1e8

Maternal and newborn mortality remain unacceptably high in sub-Saharan Africa where use of a skilled birth attendant (SBA) at delivery has remained low. Despite the recognized importance of women’s empowerment as a key determinant of maternal and newborn health, evidence from sub-Saharan Africa is more limited. Using data from the 2010 Tanzania Demographic and Health Survey (n = 4,340), this study employs a robust method–structural equation modeling (SEM)–to investigate the complex and multidimensional pathways through which women’s empowerment affects SBA use. The results show that women’s education and household decision-making are positively associated with SBA use. However, not all empowerment dimensions have similar effects. Attitudes towards sex negotiation and violence as well as early marriage are not significant factors in Tanzania. Mediation analysis also confirms the indirect effect of education on SBA use only through household decision-making. The findings underscore the utility of structural equation modeling when examining complex and multidimensional constructs, such as empowerment, and demonstrate potential causal inference to better inform policy and programmatic recommendations.

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<![CDATA[Preliminary results of identification and quantification of paclitaxel and its metabolites in human meconium from newborns with gestational chemotherapeutic exposure]]> https://www.researchpad.co/article/5c76fe5dd5eed0c484e5b96b

Objective

Cancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.

Study design

Meconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.

Results

Mean (standard deviation) levels of paclitaxel in positively screened samples were 399.9 (248.6) pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3’-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel mean levels were 105.2 (54.6) and 113.4 (48.9) pg/mg meconium, respectively.

Conclusion

Intact paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.

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<![CDATA[Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia]]> https://www.researchpad.co/article/5c6f14b9d5eed0c48467a745

Objective

Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Study design

Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008–2010 (SHIVER) and 2010–2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.

Results

244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C– 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C– 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.

Conclusions

Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.

Trial registration

www.trialregister.nl NTR2529.

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<![CDATA[Carriage and colonization of C. difficile in preterm neonates: A longitudinal prospective study]]> https://www.researchpad.co/article/5c76fe0ed5eed0c484e5b398

Background

Premature neonates (PN) present multiple risk factors for high frequencies and high levels of colonization by C. difficile, yet data is missing about this specific pediatric population. Here, we investigated PN C. difficile carriage and colonization dynamics, analyzed the impact of perinatal determinants on colonization, and characterized the isolates.

Methods

A one year longitudinal monocentric prospective cohort study was performed on 121 PN. C. difficile strains isolated from fecal samples on selective medium were identified and characterized by PCR (tpi housekeeping gene; tcdA and tcdB, and binary toxin genes), capillary gel-based electrophoresis PCR-ribotyping, and Multi-Locus Variable-number tandem-repeat Analysis (MLVA).

Results

Of the 379 samples analyzed, 199 (52%) were C. difficile culture positive with the mean levels of C. difficile colonization decreasing significantly (P = .027) over time. During hospitalization, C. difficile colonization frequency increased up to 61% with 95% of the strains belonging to both non-toxigenic PCR-ribotypes (RTs) FR082 (35%) and 032 (60%). After hospital discharge, if a higher diversity in RTs was observed, RTs FR082 and 032 remained predominant (respectively 40% and 28%). MLVA showed clonal relationship within each FR082 and 032 RTs. Ten toxigenic strains (5%) were isolated, all tcdA+/tcdB+ except for one tcdA-/tcdB+, and all being acquired after hospitalization. At 1 week, the only factors found to be linked with a higher frequency of C. difficile colonization were a higher gestational age (P = 0.006) and a higher birth weight (P = 0.016).

Conclusion

The dynamics of C. difficile colonization in PN followed a specific pattern. C. difficile colonization rapidly occurred after birth with a low diversity of non-toxigenic RTs. After hospitalization, non-toxigenic RTs diversity increased. Sporadic carriage of toxigenic strains was observed after hospitalization.

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<![CDATA[Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect]]> https://www.researchpad.co/article/5c6730e6d5eed0c484f382c7

Objective

To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders.

Methods

This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline’s criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates.

Results

Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2–3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1–7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1–0.7) and need for surfactant (OR = 0.5, CI: 0.2–0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2–3 only, RC = 6.5 days, CI: 2–11). No other outcome was affected.

Conclusions

IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.

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<![CDATA['Nasal mask’ in comparison with ‘nasal prongs’ or ‘rotation of nasal mask with nasal prongs’ reduce the incidence of nasal injury in preterm neonates supported on nasal continuous positive airway pressure (nCPAP): A randomized controlled trial]]> https://www.researchpad.co/article/5c5ca2add5eed0c48441e87c

Background

With increasing use of nCPAP, the safety and comfort associated with nCPAP have come into the forefront. The reported incidence of nasal injuries associated with the use of nCPAP is 20% to 60%. A recent meta-analysis concluded that the use of nasal masks significantly decreases CPAP failure and the incidence of moderate to severe nasal injury and stress the need for a well powered RCT to confirm their findings.

Methods

In this Open label, 3 arms, sequential, stratified randomized controlled trial, we evaluated the incidence and severity of nasal injury at removal of nCPAP when using two different nasal interfaces and in three groups (i.e. rotation group, mask continue group, prong continue group). Preterm infants with gestation ≤ 30 weeks and respiratory distress within the first 6 hours of birth and in need of CPAP were eligible for the study.

Results

Among the 175 newborns included in the study, incidence of nasal injury in mask continue group [n = 19/57 (33.3%)] was significantly less as compared to prong continue group [n = 55/60 (91.6%)] and rotation group [33/ 58 (56.9%), p value <0.0001]. Median maximum nasal injury score was significantly less in Mask continue group as compared to Prong continue group and Rotation group [Injury Score 0 (IQR 0–1) vs. Injury Score 3 (IQR 2–5) vs. Injury Score 1 (IQR 0–2), p value = <0.0001] respectively. The proportion of infants failing nCPAP was similar across the three groups.

Conclusion

nCPAP with nasal masks significantly reduces nasal injury in comparison with nasal prongs or rotation of nasal prongs and nasal masks. However, the type of interface did not affect the nCPAP failure rates.

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<![CDATA[Quality of routine facility data for monitoring priority maternal and newborn indicators in DHIS2: A case study from Gombe State, Nigeria]]> https://www.researchpad.co/article/5c57e705d5eed0c484ef490d

Introduction

Routine health information systems are critical for monitoring service delivery. District Heath Information System, version 2 (DHIS2) is an open source software platform used in more than 60 countries, on which global initiatives increasingly rely for such monitoring. We used facility-reported data in DHIS2 for Gombe State, north-eastern Nigeria, to present a case study of data quality to monitor priority maternal and neonatal health indicators.

Methods

For all health facilities in DHIS2 offering antenatal and postnatal care services (n = 497) and labor and delivery services (n = 486), we assessed the quality of data for July 2016-June 2017 according to the World Health Organization data quality review guidance. Using data from DHIS2 as well as external facility-level and population-level household surveys, we reviewed three data quality dimensions—completeness and timeliness, internal consistency, and external consistency—and considered the opportunities for improvement.

Results

Of 14 priority maternal and neonatal health indicators that could be tracked through facility-based data, 12 were included in Gombe’s DHIS2. During July 2016-June 2017, facility-reported data in DHIS2 were incomplete at least 40% of the time, under-reported 10%-60% of the events documented in facility registers, and showed inconsistencies over time, between related indicators, and with an external data source. The best quality data elements were those that aligned with Gombe’s health program priorities, particularly older health programs, and those that reflected contact indicators rather than indicators related to the provision of commodities or content of care.

Conclusion

This case study from Gombe State, Nigeria, demonstrates the high potential for effective monitoring of maternal and neonatal health using DHIS2. However, coordinated action at multiple levels of the health system is needed to maximize reporting of existing data; rationalize data flow; routinize data quality review, feedback, and supervision; and ensure ongoing maintenance of DHIS2.

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<![CDATA[The intestinal fatty acid-binding protein as a marker for intestinal damage in gastroschisis]]> https://www.researchpad.co/article/5c466552d5eed0c48451897c

Background/Purpose

We analyzed the capacity of urinary Intestinal fatty acid-binding protein (I-FABP) to quantify the degree of mucosal injury in neonates with gastroschisis (GS) and to predict the speed of their clinical recovery after surgery.

Methods

In this prospective study, we collected urine during the first 48h after surgery from neonates operated between 2012 and 2015 for GS. Neonates with surgery that did not include gut mucosa served as controls for simple GS and neonates with surgery for intestinal atresia served as control for complex GS patients. The I-FABP levels were analyzed by ELISA.

Results

Urinary I-FABP after the surgery is significantly higher in GS newborns than in control group; I-FABP in complex GS is higher than in simple GS. I-FABP can predict subsequent operation for ileus in patients with complex GS. Both ways of abdominal wall closure (i.e. primary closure and stepwise reconstruction) led to similar levels of I-FABP. None of the static I-FABP values was useful for the outcome prediction. The steep decrease in I-FABP after the surgery is associated with faster recovery, but it cannot predict early start of minimal enteral feeding, full enteral feeding or length of hospitalization.

Conclusion

Urinary I-FABP reflects the mucosal damage in gastroschisis but it has only a limited predictive value for patients’ outcome.

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<![CDATA[Length of stay following vaginal deliveries: A population based study in the Friuli Venezia Giulia region (North-Eastern Italy), 2005-2015]]> https://www.researchpad.co/article/5c37b7c6d5eed0c484490c88

Background

Lengths of hospital stay (LoS) after childbirth that are too long have a number of health, social and economic drawbacks. For this reason, in several high-income countries LoS has been reduced over the past decades and early discharge (ED) is increasingly applied to low-risk mothers and newborns.

Methods

We conducted a population-based study investigating LoS after chilbirth across all 12 maternity centres of Friuli Venezia-Giulia (FVG), North-Eastern Italy, using a database capturing all registered births in the region from 2005 to 2015 (11 years). Adjusting for clinical factors (clinical conditions of the mother and the newborn), socio-demographic bakground and obstetric history with multivariable logistic regression, we ranked facility centres for LoS that were longer than our proposed ED benchmarks (defined as >2 days for spontaneous vaginal deliveries and >3 days for instrumental vaginal deliveries). The reference was hospital A, a national excellence centre for maternal and child health.

Results

The total number of births examined in our database was 109,550, of which 109,257 occurred in hospitals. During these 11 years, the number of births significantly diminished over time, and the pooled mean LoS for spontaneous vaginal deliveries in the whole FVG was 2.9 days. There was a significantly decreasing trend in the proportion of women remaining admitted more than the respective ED cutoffs for both delivery modes. The percentage of women staying longer that the ED benchmarks varied extensively by facility centre, ranging from 32% to 97% for spontaneous vaginal deliveries and 15% to 64% for instrumental vaginal deliveries. All hospitals but G were by far more likely to surpass the ED cutoff for spontaneous deliveries. As compared with hospital A, the most significant adjusted ORs for LoS overcoming the ED thresholds for spontaneous vaginal deliveries were: 89.38 (78.49–101.78); 26.47 (22.35–31.36); 10.42 (9.49–11.44); 10.30 (9.45–11.21) and 8.40 (7.68–9.19) for centres B, D, I, K and E respectively. By contrast the OR was 0.77 (95%CI: 0.72–0.83) for centre G. Similar mitigated patterns were observed also for instrumental vaginal deliveiries.

Conclusions

For spontaneous vaginal deliveries the mean LoS in the whole FVG was shorter than 3.4 days, the average figure most recently reported for the whole of Italy, but higher than other countries’ with health systems similar to Italy’s. Since our results are controlled for the effect of all other factors, the between-hospital variability we found is likely attributable to the health care provider itself. It can be argued that some maternity centres of FVG may have had ecocomic interest in longer LoS after childbirth, although fear of medico-legal backlashes, internal organizational malfunctions of hospitals and scarce attention of ward staff on performance efficiency shall not be ruled out. It would be therefore important to ensure higher level of coordination between the various maternity services of FVG, which should follow standardized protocols to pursue efficiency of care and allow comparability of health outcomes and costs among them. Improving the performance of FVG and Italian hospitals requires investment in primary care services.

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