Antenatal Betamethasone in Late Preterm Deliveries

http://www.nejm.org/doi/full/10.1056/NEJMoa1516783?query=featured_home

multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.

Results

The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).

Conclusions

Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications.

Hypoglycemia management podcast

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

Nature Communications 6, Article number: 8977 doi:10.1038/ncomms9977
http://www.nature.com/ncomms/2015/151127/ncomms9977/full/ncomms9977.html
www.sciencedaily.com/releases/2016/01/160115140128.htm

The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3−/− mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β:IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.

Association of Coffee Consumption with Total and Cause-Specific Mortality in Three Large Prospective Cohorts

CIRCULATIONAHA.115.017341 Published online before print November 16, 2015,
doi: 10.1161/CIRCULATIONAHA.115.017341

http://circ.ahajournals.org/content/early/2015/11/10/CIRCULATIONAHA.115.017341.abstract

Background—The association between consumption of caffeinated and decaffeinated coffee and risk of mortality remains inconclusive.

Methods and Results—We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 74,890 women in the Nurses' Health Study (NHS), 93,054 women in the NHS 2, and 40,557 men in the Health Professionals Follow-up Study. Coffee consumption was assessed at baseline using a semi-quantitative food frequency questionnaire. During 4,690,072 person-years of follow-up, 19,524 women and 12,432 men died. Consumption of total, caffeinated, and decaffeinated coffee were non-linearly associated with mortality. Compared to non-drinkers, coffee consumption one to five cups/d was associated with lower risk of mortality, while coffee consumption more than five cups/d was not associated with risk of mortality. However, when restricting to never smokers, compared to non-drinkers, the HRs of mortality were 0.94 (0.89 to 0.99) for ≤ 1 cup/d, 0.92 (0.87 to 0.97) for 1.1-3 cups/d, 0.85 (0.79 to 0.92) for 3.1-5 cups/d, and 0.88 (0.78 to 0.99) for > 5 cups/d (p for non-linearity = 0.32; p for trend < 0.001). Significant inverse associations were observed for caffeinated (p for trend < 0.001) and decaffeinated coffee (p for trend = 0.022). Significant inverse associations were observed between coffee consumption and deaths due to cardiovascular disease, neurological diseases, and suicide. No significant association between coffee consumption and total cancer mortality was found.

Conclusions—Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.

More ...
reports the effect is clear only among those who drink coffee and “never smoked.” Among those, there was a 6% to 8% lower death rate connected to drinking up to 3 cups daily, and a 15% lower rate among those who drank 3 to 5 cups, and a 12% lower rate among those who drank over 5 cups daily. One possibility suggested is that coffee drinkers “drink less soda,” while it is also suggested that the lignans and chlorogenic acid in coffee “could reduce inflammation and help control blood sugar,” and so “reduce the risk of heart disease,” which was 10% lower among coffee drinkers. In addition, coffee drinkers had a 9% to 37% lower rate of death from “neurological diseases such as Parkinson’s and dementia.” They also had “between 20% and 36% lower rates of suicide.”

Vivaha Bhojanambu-My attempt

Slow Advancement of Enteral Feeds in VLBW Infants-Is It Harmful?

Cochrane Database Syst Rev. 2015 Oct 15;10:CD001241

Morgan J, Young L, McGuire W.

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001241.pub6/abstract

MAIN RESULTS:

We identified nine randomised controlled trials in which 949 infants participated. Most participants were stable preterm infants with birth weights between 1000 and 1500 g. Fewer participants were extremely preterm, extremely low birth weight, or growth-restricted. The trials typically defined slow advancement as daily increments of 15 to 24 mL/kg and faster advancement as 30 to 40 mL/kg. Meta-analyses did not show statistically significant effects on the risk of NEC (typical RR 1.02, 95% CI 0.64 to 1.62; typical RD -0.00, 95% CI -0.03 to 0.03) or all-cause mortality (typical RR 1.18, 95% CI 0.90 to 1.53; typical RD 0.03, 95% CI -0.02 to 0.08). Slow feeds advancement delayed the establishment of full enteral nutrition by one to five days and increased the risk of invasive infection (typical RR 1.46, 95% CI 1.03 to 2.06; typical RD 0.07, 95% CI 0.01 to 0.13; number needed to treat for an additional harmful outcome 14, 95% CI 8 to 100).

AUTHORS' CONCLUSIONS:

The available trial data suggest that advancing enteral feed volumes at daily increments of 30 to 40 mL/kg (compared to 15 to 24 mL/kg) does not increase the risk of NEC or death in VLBW infants. Advancing the volume of enteral feeds at slow rates results in several days of delay in establishing full enteral feeds and increases the risk of invasive infection. The applicability of these findings to extremely preterm, extremely low birth weight, or growth-restricted infants is limited. Further randomised controlled trials in these populations may be warranted to resolve this uncertainty.

Neonatal brain MRI: how reliable is the radiologist’s eye?

http://link.springer.com/article/10.1007%2Fs00234-015-1609-2


Introduction

White matter (WM) analysis in neonatal brain magnetic resonance imaging (MRI) is challenging, as demonstrated by the issue of diffuse excessive high signal intensity (DEHSI). We evaluated the reliability of the radiologist’s eye in this context.


Methods

Three experienced observers graded the WM signal intensity on axial T2-weighted 1.5T images from 60 different premature newborns on 2 occasions 4 weeks apart with a semi-quantitative classification under identical viewing conditions.


Results

The intra- and inter-observer correlation coefficients were fair to moderate (Fleiss’ kappa between 0.21 and 0.60).


Conclusion

This is a serious limitation of which we need to be aware, as it can lead to contradictory conclusions in the challenging context of term-equivalent age brain MRI in premature infants. These results highlight the need for a semiautomatic tool to help in objectively analyzing MRI signal intensity in the neonatal brain.

Digital Stethoscope Attachment-EKO

https://ekodevices.com/whitepapers/Eko_for_Primary_Care_Whitepaper.pdf

It is small digital attachment to any stethoscope, and it instantaneously coverts an analog to a digital mode. It can record, amplify, and show the visualization of heart sounds.

Should we follow Resolved Antenatal Hydronephrosis?

http://link.springer.com/article/10.1007%2Fs00467-015-3080-z

Background

Prenatal ultrasonography has greatly enhanced detection of congenital genitourinary abnormalities. However, although persistent prenatal hydronephrosis (PPH) is typically imaged and followed postnatally, it remains unclear if prenatal hydronephrosis that resolves in utero (RPH) should be similarly managed. We determined postnatal abnormalities associated with RPH and compared these to those associated with PPH.

Methods

We performed a retrospective review of all consecutive patients evaluated for prenatal hydronephrosis over 24 months. Patients were followed prenatally with serial ultrasounds and postnatally with ultrasonography and a voiding cystourethrogram.

Results

Of the consecutive 165 patients enrolled in the study, 72 had RPH. The average prenatal anterior–posterior renal pelvis length was significantly longer in patients with PPH (5.5 mm) than in those with RPH (4.9 mm) (p = 0.01). Recurrent postnatal hydronephrosis occurred in 44 % of patients with RPH, with eventual resolution in 34 % of those affected. In comparison, 29 % of PPH cases resolved postnatally. Mean time to resolution was statistically shorter for PPH (116 days) than for RPH (175 days) (p = 0.01). Seven PPH patients required surgery, while no RPH patients needed intervention (difference was statistically significant).

Conclusions

A significant number of RPH children had postnatal hydronephrosis. Despite a slower resolution time, no children with RPH required intervention. Although RPH may recur postnatally, the significantly lower chance of intervention being required suggests that these children may not require postnatal imaging.

Metanalysis of Probiotics Advantage in Reducing NEC in VLBW Infants

Yet another confirmation of utility of probiotics in VLBW infants
http://www.jpedsurg.org/article/S0022-3468(15)00362-0/abstract?rss=yes

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants, affecting ~6–7% of very-low-birth-weight (VLBW) infants. Early intervention and aggressive treatment has improved clinical outcomes, but considerable morbidity continues to accrue to NEC survivors. This meta-analysis examines the impact of probiotics on the incidence of NEC and complications among VLBW infants.

Methods

A comprehensive literature search for all published randomized control trials (RCTs) assessing the use of probiotics to prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966–2014). The incidences of NEC, sepsis, overall mortality, and time to reach full enteral feeds were analyzed.

Results

20 RCTs involving 5982 preterm VLBW infants were analyzed. Risk of NEC was reduced by 49.1% (RR = 0.509; 95% CI, 0.385–0.672; p < 0.001), and overall mortality by 26.9% among infants receiving probiotics (RR = 0.731; 95% CI, 0.577–0.926; p = 0.009). An 8.1% reduction in sepsis was also observed in infants receiving probiotics (RR = 0.919; 95% CI, 0.823–1.027; p = 0.137). Time to reach full enteral feeds was reduced by 1.2 days among infants receiving probiotics (MD: −1.217; 95% CI, −2.151 to −0.283; p = 0.011).

Conclusion

The use of probiotic supplementation in preterm VLBW infants is associated with a significant reduction in the risk of NEC and overall mortality. Additional studies are required to determine the optimal genus, species, and dose of probiotic.

Evaluating Persistent Hypoglycemia-Recommendations

http://www.jpeds.com/article/S0022-3476(15)00358-3/fulltext

For infants and younger children who are unable to reliably communicate symptoms, suggestted evaluation and management only of those whose Plasma Glucose concentrations are documented by laboratory quality assays to be below the normal threshold for neurogenic responses (<60 mg/dL [3.3 mmol/L]). GRADE 2+++0. Free fatty acids cannot be used by brain as fuel, whereas, Beta Hydroxy Buteric Acid (BOHB)and lactate can be used by the brain. When glucose level is <60mg/dl, measure lactate, FFA, BOHB, and HCO3 Insulin, cpeptide, GH (growth hormone)cortisol, acyl carnitine, and free carnitine may need to be measured.

HyperInhyperinsulinemic states--LOW BOHB, and FFA will be seen, and HCO3 will be normal.

In Fatty Acid Oxidation defects--- LOW BOHB, but INCREASED FFA, with normal HCO3 will be seen.

In Gluconeogenesis defects: LOW HOCO3, and INcreased Lactate is noted.

In GH, or Cortisol deficiency-Low HCO3, and Increased BOHB.

An exaggerated glycemic response (>30 mg/dL [>1.7 mmol/L]) is nearly pathognomonic of hyperinsulinism.


Because plasma insulin concentration is sometimes not above the lower limit of detection,

it is important to include the following tests when assessing the possibility of hypoglycemia due to hyperinsulinism: plasma BOHB and FFA (both inappropriately low; BOHB <1.5 mmol/L [<15 mg/dL] and FFA <1.0-1.5 mmol/L [<28-42 mg/dL]), and an increased glycemic response to glucagon. For neonates with a suspected congenital hypoglycemia disorder and older infants and children with a confirmed hypoglycemia disorder, recommend that the goal of treatment be to maintain a PG concentration >70 mg/dL.

For high-risk neonates without a suspected congenital hypoglycemia disorder, we suggest the goal of treatment be to maintain a PG concentration >50 mg/dL (>2.8 mmol/L) for those aged <48 hours and >60 mg/dL (>3.3 mmol/L) for those aged >48 hours.

Automating inspired oxygen to targeted SpO2 in preterm infants

Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study

Mithilesh Lal1, Win Tin1,and Sunil Sinha



Aim


To evaluate the efficacy of automated control of the fraction of inspired oxygen (FiO2) in comparison to manual FiO2 control in maintaining target pulse oxygen saturation (SpO2) range.


Methods


Crossover physiologic study involving preterm infants requiring mechanical ventilation and supplemental oxygen. Each infant was studied for 2 consecutive 12-hour in a random sequence. Outcome measures included the proportion of time with SpO2 within and outside the target range of 90-95%, extreme hypoxaemia (<80%) and hyperoxaemia (≥98%).


Results


Complete dataset was available in 27 infants. The percentage of time (median, IQR) within the target range was higher during automated control 72.8 (58.8-82.6) compared to manual control 59.6 (49.3-73.3), p=0.031. Corresponding reduction in percent time below the target range was 18.1 (12.7-23.6) versus 25.9 (17.8-30.7), p=0.028, and above the target range 4.8 (3-16) versus 10.1 (6.4-22.5), p=0.026. Median (IQR) percent time spent with severe hypoxaemia (SpO2<80%) and severe hyperoxaemia (SpO2≥98%) were 1.3 (0.1-2.9) versus 3.2 (1.4-6.1), p= 0.022 and 0.08 (0.05-0.36) versus 1.7 (0.7-6.8), p=0.001 respectively. Median number of manual adjustments of FiO2 per 12-hour was 0 and 63 respectively.


Conclusion


Automated control of FiO2 significantly improved compliance of oxygen saturation targeting and significantly reduced exposure to hypoxaemia as well as hyperoxaemia.

Strategies in PPROM in Preterm Infants

There is usually pulmonary hypoplasia with relatively normal compliance.
Strategy: Use low PEEP, as high PEEP can interfere with venous return, and cardiac output.

There is usually pulmonary vasoconstriction, and hypertension.
Strategy: Keep PaO2 above 50mm Hg.
Frequent Echocardiograms to evaluate shunting across PDA.
Use iNO as needed.

Ventricular dysfunction, and or systemic hypotension.
Strategy: May use volume and or inotropics (dobutamine if LV dysfunction, and dopamine if systemic hypotension)
Use inotropes if there is LV systolic dysfunction with or without left atrial dialatation before using iNO to avoid pulmonary edema.
Source: Journal of Pediatrics, 2015, Dr. de Waal, and Dr. Kluckow.

ESPGHAN: Irish scientists have identified a novel milk-derived component that may help resolve cow’s milk protein allergy

http://www.merckmedicus.com/conference-reports/10/ESPGHAN-Irish-scientists-have-identified-a-novel-milk-derived-component-that-may-help-resolve-cow-s-milk-protein-allergy?


presented at the Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition



Irish scientists have identified a novel milk-derived component that can specifically suppress secretion of IL-4 by differentiated Th2 cells. The presence of such a component in hypoallergenic infant formula may act to suppress the over-activated Th2 response associated with allergy and find usefulness in enhancing resolution of cow’s milk protein allergy. Researchers at the Immunomodulation Group, Dublin City University, and colleagues presented their paper at ESPGHAN, held in May in Amsterdam.

In Europe, 20% to 30% of infants are diagnosed with an atopic disease. The majority of first atopic responses are directed towards food proteins that are observed during the first months of life, such as cows milk protein. Cows milk protein allergy (CMPA) affects 2.2% to 7.5% of infants worldwide and is a growing public health problem in Western Europe and the USA. Existing hypoallergenic formula solutions adopt avoidance strategies such as the extensive hydrolysis of whey or casein proteins (using proteolytic bacteria or enzymes). However, allergic responses are associated with a dominant T helper type 2 (Th2) response, which plays a key role in triggering IgE production by B cells. The aim of the Irish study was to assess whether novel milk-derived component can suppress Th2 responses which may enhance resolution of CMPA and lower the risk of developing a further allergy.

Murine spleenocytes were isolated from the spleens of 8-14 week old BALB/c mice and purified for CD4+ T-cells using magnetic negative isolation. After extensive cell activation and differention, The novel milk-derived component was added during T helper cell differentiation. Th1 and Th2 subsets were confirmed using ELISA analysis of cytokine production after 3 days. The novel milk-derived component specifically suppressed the secretion of IL-4 from differentiated Th2 cells in a dose dependent manner. A regenerated form of the novel milk-derived component also had the same effect. Interestingly, the novel component had no effect on Th1 cells and the level of secretion of IFNγ was not affected by the presence of the component. This suggests that the component specifically suppresses Th2 responses.

Oh Mother!

Oh mother of mine
How can I describe you in a line
For you are so divine
And makes us feel always on cloud nine
Whenever our lethargy makes you whine
For you made us so with your intoxicating love wine
With your affection you entwine
With devotion that you combine
Our character you refine
You seek pleasure when we shine
We are always blessed in mother’s shrine

Pradeep Alur.