The NeoUpdates

Nov 15, 2009 Volume 1 (Number 1)

A Monthly Electronic Bulletin on Neonatal and Perinatal medicine
This bulletin is an attempt to summarize the current research (on monthly basis) in the field of neonatal and perinatal medicine. I have tried to summarize the researches in simple language and added results of systemic review on the same topics on few significant issues. But, results of these studies cannot be directly utilized! I have tried to sort out this issue by adding an editorial “how do current researches would change my practice?” I will be grateful for any sort of critical comments or suggestions to improve current format of the The NeoUpdates, so that it can be more useful for the readers. I would appreciate your preference for email for all kinds of thought exchanges.

This bulletin will be circulated electronically (email) and well as in text format.
As electronic format would be more convenient, cost effective, and eco-friendly; we would discontinue text format after few months. Those who are receiving only text format please email me your details, so that I can include you in mailing list of next issues of the The NeoUpdates.


Dr Satish Mishra
MD Pediatrics DM Neonatology (AIIMS, New Delhi) Ex-Senior Research Associate (CSIR, New Delhi) Ex-Senior Research Officer (WHO; PGIMER, Chandigarh)

Clinic Add: E – 4/94, 10 No. Stop, Arera Colony, Bhopal – 462016 Email:, Mobile: 9407533300

Disclaimer: Author has no commercial interest with the The NeoUpdates bulletin. This bulletin is solely for increasing academic discussion among young pediatricians & obstetricians.


Perinatal Medicine
Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis
Retrospective analysis of pregnancy outcome of 1898 women from four regions of US revealed that infants born to female survivors of childhood and adolescent cancer were not at increased risk of malformations or death. However, there was increased occurrence of preterm delivery and low birth weight suggesting close monitoring of these pregnant women.

(Mueller BA et al. Arch Pediatr Adolesc Med. 2009 Oct;163:879-86.)

A multicenter, randomized trial of treatment for mild gestational diabetes
A multicenter trial on 958 pregnant women between 24th to 31st week of gestation with mild gestational diabetes (defined as an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per decilitre) revealed that treatment of these women (dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary) reduce the risks of fetal overgrowth (7.1% vs. 14.5%), shoulder dystocia (1.5% vs. 4.0%), cesarean delivery (26.9% vs. 33.8%), and hypertensive disorders in mother (8.6% vs. 13.6%).

Landon MB et al. N Engl J Med. 2009 Oct 1;361(14):1339-48.

Current status on treatment for gestation diabetes
Gestational diabetes (GDM) affects 3% -6% of all pregnancies. These women are intensively monitored and managed by dietary modifications and insulin. This cochrane review included eight trials (n=1418) looking at intensive vs. conservative treatment of gestational diabetes on pregnancy outcome. Mothers under intensive treatment of GDM had lesser incidence of pre-eclampsia (RR 0.65, 95% CI 0.48 to 0.88) and perinatal morbidity (death, shoulder dystocia, bone fracture and nerve palsy) (RR 0.32, 95% CI 0.14 to 0.73). There was reduction in proportion of neonates >4000 g and LFD neonates of mothers receiving specific treatment for GDM compared to routine ANC. However, caesarean section rate was not affected by specific treatment of GDM and, infect, there was higher incidence of labor induction among these women ((RR 1.33, 95% CI 1.13 to 1.57). Specific treatment including dietary advice and insulin for mild GDM reduces the risk of maternal and perinatal morbidity. However, it is associated with higher risk of labour induction.

Treatments for gestational diabetes
Alwan N et al. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD003395


Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania
Vitamin D is a strong immunomodulator and may protect against adverse pregnancy outcomes, mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), and child mortality. In 884 women participating in vitamin D supplementation trial no association was observed between maternal vitamin D status and adverse pregnancy outcomes, including low birth weight and preterm birth. However, low maternal vitamin D status was associated with 50% higher risk of MTCT of HIV at 6 weeks of age. Children born to women with a low vitamin D level had a 61% higher risk of dying during follow-up. However, this was observational study and if found to be efficacious in randomized trials, vitamin D supplementation could prove to be an inexpensive method of reducing the burden of HIV infection and death among children, particularly in resource-limited settings

Mehta S et al. J Infect Dis. 2009 Oct 1;200(7):1022-30.

Neonatal Medicine
Moderate hypothermia to treat perinatal asphyxial encephalopathy
Yet again, a randomized trial (TOBY trial) on whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy published in NEJM on Oct 1. With huge sample size study revealed that though induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability (RR 0.86; 95% CI, 0.68 to 1.07), but it resulted in improved neurologic outcomes in survivors (RR 0.67; 95% CI, 0.47 to 0.96).

Azzopardi DV. N Engl J Med. 2009 Oct 1;361(14):1349-58.

Current status on Moderate hypothermia to treat moderate to severe HIE
There is evidence from existing trials (eight, n=638) that in term infants with moderate to severe hypoxic-ischaemic encephalopathy therapeutic hypothermia significantly reduces the mortality without increasing major disability in survivors (RR 0.74; 95% CI 0.58, 0.94). The benefits of cooling on survival and neurodevelopment outweigh the short-term adverse effects (an increase in the need for inotrope support of borderline significance and a significant increase in thrombocytopenia). Cooling for newborns with hypoxic ischaemic encephalopathy Jacobs S. Cochrane Database of Systematic Reviews 2007, Issue 4


**Transcutaneous bilirubinometry reduces the need for blood sampling in neonates with visible jaundice

In a RCT enrolling 617 jaundiced term and late-preterm neonates, neonates were randomized to either transcutaneous bilirubinometry (TcB) or protocol-based visual assessment of bilirubin (VaB) for deciding the need for blood sampling to assay STB. Blood sampling was done if the assessed bilirubin by either method was ≥80% of phototherapy cutoff (AAP 2004). Study revealed that need for blood sampling to assay STB was 34% lower (95% CI: 10% to 51%) in the TcB group compared with VaB group (17.5% vs 26.4%). Although TcB was found to be more accurate compared to VaB, systematic VaB had significant correlation with measured STB till 15 mg/dL.

S Mishra et al. Acta Pædiatrica 2009 Nov; 98: 1916–1919.

**Limb splinting for intravenous cannulae in neonates: a randomised controlled trial

In this RCT (n=54) authors assessed the efficacy of peripheral intravenous (IV) cannula site joint immobilisation by splint application on functional duration of peripheral IV cannula in neonates. Functional duration of a peripheral IV cannula measured as interval from time of insertion to the development of predefined sign of removal (extravasation, blockage, inflammation). Study revealed joint immobilisation with splint at cannula site did not improve the functional duration of peripheral IV cannula.

SS Dalal et al. Arch Dis Child Fetal Neonatal Ed 2009 Oct; 94(6):F394-6.

**Does Measuring the Changes in TcB Value Offer Better Prediction of Hyperbilirubinemia in Healthy Neonates?

Study evaluated the diagnostic value of changes in transcutaneous bilirubin (TcB) levels for prediction of subsequent hyperbilirubinemia in healthy term and late-preterm neonates. Two TcB determinations were performed for all enrolled neonates (N = 358). The first assessment (TcB1) was performed at 24 ± 6 hours of age, followed by a second (TcB2) 12 hours later. Changes in TcB levels were calculated. Study revealed that single TcB measurements at 30 to 48 hours predict hyperbilirubinemia with a reasonably high degree of accuracy. Changes in TcB levels do not offer any added clinical benefit.

SS Dalal et al. Pediatrics 2009 Oct; 124 (5): e851-e857
** Studies from India.


Improvement of short- and long-term outcomes for very low birth weight infants: Edmonton NIDCAP trial
Developmental care is a broad category of interventions designed to minimize the stress of the NICU environment. These interventions may include elements such as control of external stimuli (vestibular, auditory, visual, tactile), clustering of nursery care activities, and positioning or swaddling of the preterm infant. Individual strategies have also been combined to form programs, such as the 'Newborn Individualized Developmental Care and Assessment Program' (NIDCAP). Canadian study enrolling a total of 111 neonates randomized to either Newborn Individualized Developmental Care and Assessment (NIDCAP) or standard NICU care reported that NIDCAP group infants had reduced length of stay (median: NIDCAP: 74 days; control: 84 days; P = .003) and incidence of chronic lung disease (NIDCAP: 29%; control: 49%; odds ratio: 0.42, 95% CI: 0.18-0.95). At 18 months of adjusted age, NIDCAP group infants had less disability, specifically mental delay (NIDCAP: 10%; control: 30%; odds ratio: 0.25, 95% CI: 0.08-0.82).

Peters KL et al. Pediatrics. 2009 Oct;124:1009-20.

Hazardous co-sleeping environments and risk factors amenable to change: casecontrol study of SIDS in south west England.
In a case control study from England including 80 SIDS infants, co-sleeping with parents especially on sofa, recent parental use of alcohol, use of pillow for infant, and prematurity are the found to be significant risk factors for SIDS.

Blair PS. BMJ. 2009 Oct 13;339:b3666.

Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.
In a multicenter, double-blind, randomized trial conducted in 11 Italian tertiary NICUs enrolling 472 VLBW infants bovine lactoferrin (BLF) alon or in combination with the probiotic Lactobacillus rhamnosus GG (LGG) reduced the incidence of a first episode of late-onset sepsis (RR 0.34; 95% CI, 0.17-0.70). Infants in intervention group received BLF (100 mg/d) alone or BLF plus LGG (6 x 109 colony-forming units/d) from birth until day 30 of life (day 45 for neonates <1000 g at birth).

Manzoni P et al. JAMA. 2009 Oct 7;302(13):1421-8.


Antibiotic prophylaxis and recurrent urinary tract infection in children

A large multicenter RCT from Australia confirmed that long-term, low-dose trimethoprimsulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) was associated with a decreased number of urinary tract infections (HR, 0.61; 95% CI, 0.40 to 0.93) in predisposed children (e.g. vesicoureteral reflux). A total of 576 children were randomized in to either treatment or placebo groups after first diagnosis of urinary tract infection and treatment was continued for 12 months.

Craig JC et al. N Engl J Med. 2009 Oct 29;361(18):1748-59.

Cochrane review on Long-term antibiotics for preventing recurrent urinary tract infection in children including eight studies (618 children) reported compared to placebo/no treatment, antibiotics reduced the risk of repeat positive urine culture (RR 0.44, 95% CI 0.19 to 1.00; RD -30%, 95% CI -56% to -4%). No side effects were reported. Nitrofurantoin was reported to be more effective than trimethoprim, however, with more adverse effects.

Long-term antibiotics for preventing recurrent urinary tract infection in children Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001534.

Efficacy and safety of intermittent preventive treatment with sulfadoxinepyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials

This was a systematic review of the studies evaluating safety and efficacy of intermittent preventive treatment (IPT) for malaria control in infants in Africa. Pooled data of six studies providing data for 7930 infants revealed that IPT (sulfadoxine-pyrimethamine or placebo administered at the time of routine vaccination) had protective efficacy of 30% against clinical malaria, 21% against risk of anemia, and 38% against hospital admission associated with malaria parasitemia. Adverse effects were not significantly different between the two groups. Overall IPT with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control.

Aponte JJ et al. Lancet. 2009 Oct 31;374(9700):1533-42.


How do current researches would change my practice?
Treatment of mild gestational diabetes was always a dilemma to me. Current research as well as data from cochrane systematic review suggests treating these women would significantly reduce perinatal complications. Now onward I will treat pregnant women even with mild gestational diabetes. Treatment, however, may very form dietary advice to insulin. I will also keep close watch on pregnant women who survived from childhood cancers. As of now data strongly suggest that moderate hypothermia, at least in western setting with facility of high-tech devices and intensive monitoring, reduces the mortality and improve long term neurological outcome. However, feasibility may be an issue (in view of unavailability of low tech cost-effective devices). Secondly, non-uniformity in selection criteria of eligible neonates, lack of trained nursing staff in most of the NICUs, lack of facility for intensive objective monitoring, etc. are other issue precluding the use of hypothermia in most of Indian NICU settings. AIIMS and various other institutes in the country are planning/conducting trial on low-tech cooling devices, which may soon be available in the country. However, one point is very clear in my mind, hyperthermia definitely increase the severity of hypoxic-ischimic insult in the brain. So, till facility for cooling these neonates becomes available, I will at least prevent hyperthermia in neonates with HIE and keep these babies at lower side of euthermic range. I know that transcutaneous bilimeter measurement (TcB) is a good alternate to serum total bilirubin (STB) assay as a screening tool at low to moderate level of bilirubinemia (≤15 mg/dL). Current research also suggests that as compared to systematic visual assessment of bilirubin (VaB), TcB reduces the need for blood sampling to confirm STB. Also, as protocolbased VaB require more expertise, TcB being an objective tool, may be a better option for pre-discharge assessment of bilirubin and can easily be used by my nursing staff. Till now I usually think that taking two measurements of STB/TcB and calculating rate of rise in serum bilirubin may be a better predictor of subsequent hyperbilirubinemia. However, current research suggest that single TcB measurements at 30 to 48 hours age (predischarge) and plotting it on hour-specific bilirubin nomogram is as good for prediction of hyperbilirubinemia (requirement of phototherapy, AAP 2004). I will utilize this information for pre-discharge risk assessment in my neonates. My nursing staff always complaint me of excess work in NICU. I used to ask them for intravenous (IV) cannula site joint immobilisation to increase the functional duration of peripheral IV cannula. However, as this practice increases the work of nursing staff and do not add significant benefit, I would individualize this practice in my NICU. Instead, I may incorporate Newborn Individualized Developmental Care and Assessment practices like such as control of external stimuli (vestibular, auditory, visual, tactile), clustering of nursery care activities, and positioning or swaddling of the preterm infant in mu NICU. In addition, in my pre-discharge counselling, along with routine counselling, I will emphasize on hazards of cosleeping with parents especially on sofa, recent parental use of alcohol, use of pillow for infant, etc. 7|Page

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