The NeoUpdates

Dec 15, 2009 Volume 1 (Number 2)

A Monthly Electronic Bulletin on Neonatal and Perinatal medicine

Perinatal Medicine

Prior Adverse Pregnancy Outcome and the Risk of Stillbirth Authors analyzed a population-based cohort, from 1967 to 2005 from the Medical Birth Registry of Norway, to estimate whether a history of fetal growth restriction, abruptio placentae, preeclampsia, or live preterm birth is associated with excess risk of stillbirth in subsequent pregnancy. Analysis revealed, after preterm births with gestational age 22–27, 28–32, and 33–36 weeks, odd of stillbirth were 5.7 (95% CI 4.2–7.6), 2.6 (95% CI 2.1–3.3), and 1.7 (95% CI 1.5–1.9), respectively. Odds ratios of stillbirth subsequent to pregnancies with SGA, preeclampsia, and abruptio placentae were 1.7 (95% CI 1.6–1.9), 1.6 (95% CI 1.5–1.9), and 2.8 (95% CI 2.2–3.5), respectively, and increased with severity of the conditions. Gestational age below 33 weeks with preeclampsia or SGA carried 6–9 and 6–13 fold effects on later stillbirth, respectively. Men who fathered a pregnancy with preterm preeclampsia were significantly more likely to father a stillbirth in another woman (OR 2.4, 95% CI 1.1–5.5).

Svein R et al. Obstetrics & Gynecology 2009; 114:1259-70.

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk
Volumetric MRI evaluation of 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term subjects revealed decreased regional cortical grey-matter (GM) and white-matter (WM) in preterm children. Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group.

Soria-Pastor S et al. Pediatrics. 2009;124: e1161-e1170.
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The PREM score: a graphical tool for predicting survival in very preterm births
Based on data of 4838 preterm neonates (22-31 weeks’ gestation), Cole and colleagues developed a logistic regression model for prediction of survival to term for these neonates. They used gestation, birth weight for gestation and base deficit from umbilical cord blood for developing this tool. They found that gestation was by far the most powerful predictor of survival to term, and as few as 5 extra days can double the chance of survival. Weight for gestation also had a powerful but non-linear effect on survival, with weight between the median and 85th centile predicting the highest survival. Using this information survival can be predicted almost as accurately before birth as after, although base deficit further improves the prediction. This scoring system may not be useful for predicting the survival of individual neonate, but, can be used to balance risk at entry into a controlled trial and to adjust for differences in “case mix” when assessing the quality of perinatal care.

Cole TJ et al. Arch Dis Child Fetal Neonatal Ed 2010;95:F14-F19.

Pregnancy Outcomes from the Pregnancy Registry of a Human Papillomavirus Type 6/11/16/18 Vaccine
This postmarketing surveillance data-analysis of 517 pregnant women exposed to human papillomavirus (HPV) type 6/11/16/18 vaccine on pregnancy outcomes (ie, live births, abortions, fetal deaths, and congenital anomalies) did not reveal any adverse effect. Overall rate of spontaneous abortions and major birth-defects were not greater than the unexposed population rates. However, although no adverse signals have been identified to date, the HPV6/11/16/18 vaccine is not recommended for use in pregnant women.

Adrian D et al. Obstetrics & Gynecology 2009; 114(6):1170-1178.

Pregnancy and Infant Outcomes in the Clinical Trials of a Human Papillomavirus Type 6/11/16/18 Vaccine: A Combined Analysis of Five RCTs
Combined analysis of the pregnancy outcomes for women enrolled in five phase III clinical studies of the prophylactic quadrivalent human papillomavirus 6/11/16/18 vaccine enrolling 20,551 women aged 15-45 did not reveal any significant differences in the proportions of pregnancies resulting in live birth, fetal loss, or spontaneous abortion. However, currently vaccination is not recommended during pregnancy (pregnancy category B medication).

Suzanne MG et al. Obstetrics & Gynecology 2009; 114(6): 1179-1188.

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Neonatal Medicine

Chlorhexidine maternal-vaginal and neonate body wipes for prevention of early onset sepsis
Sepsis is one of the most common causes of early neonatal mortality. Use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries. The PoPS trial team assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus. In 8011 pregnant women were randomly assigned to chlorhexidine vaginal wipes or external genitalia water wipes during active labour and their 8129 newborn babies were assigned to full-body (intervention group) or foot (control group) washes with chlorhexidine at birth. Primary outcome, the rate of early onset neonatal sepsis (within 72 h of delivery), was not different between the two groups [chlorhexidine 141 (3%) of 4072 vs control 148 (4%) of 4057; p=0 65]. Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine [217 (54%) of 401] and control groups [234 (55%) of 429] were not different (efficacy −0 05%, 95% CI −9 5 to 7 9).

Cutlandet CL et al (the PoPS Trial Team). The Lancet 2009;374:1909-16.

Does skin cleansing with chlorhexidine affect skin condition, temperature and colonization in hospitalized preterm low birth weight infants?
In a randomized clinical trial enrolling 60 stable preterm neonates admitted in a health facility, Sankar et al demonstrated that single skin cleansing with 0.25% chlorhexidine reduced axillary-skin colonization at 24 h after the intervention. They monitored the temperature and skin condition score of the enrolled neonates and did not find any adverse affect on skin condition or temperature.

Sankar MJ et al. Perinatol. 2009;29:795-801.

Energy Expenditure for Breastfeeding and Bottle-Feeding Preterm Infants
In this study from Israel, authors demonstrated that there was no difference in resting energy expenditure (REE) when infants were breast fed versus bottle-fed. Although, the duration of feeding was significantly longer for breastfeeding than for bottle-feeding (20.1±7.9 vs 7.8±2.9 minutes; P<.0001), longer feeding times at the breast did not increase REE. Authors conjectured that it is safe to recommend feeding at the breast for infants born at >32 weeks when they can tolerate oral feeding.

Berger I et al. Pediatrics 2009; 124: e1149-e1152.

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Maternal IgG anti-A and anti-B titres predict outcome in ABO-incompatibility in the neonate
Study was conducted at Oslo University Hospital with aim to evaluate predictors for risk of severe hyperbilirubinemia and kernicterus in ABO-incompatible neonates with emphasize on maternal IgG antiA/B titres. Of 253 neonates born to blood group O women in labour, 72 (38.7%) had blood group either A or B. Of these 20 neonates received at least one immunoglobulin treatment. In multivariate analysis, maternal antibody-titre was the only significant predictor for immunoglobulin treatment (p < 0.0001), and duration of phototherapy (p < 0.0001). The need for invasive treatment increased sharply for antibody titres ≥512. Receiver operating characteristic analyses demonstrated that titres ≥512 had a sensitivity of 90% and a specificity of 72% for predicting immunoglobulin treatment and thus severe hyperbilirubinemia.

Bakkeheim E et al. Acta Paediatrica 2009;99:1896-1901.

Perceived breast milk insufficiency in mothers of neonates hospitalized in neonatal intensive care unit
Mathur NB et al prospectively followed a group of neonates whose mothers were willing to breastfeed their babies to study the frequency of perceived breast milk insufficiency in mothers of hospitalized neonates. Incidence of perceived breast milk insufficiency in their study was 68%. All mothers who perceived breast milk insufficiency could be helped by lactation management and exclusively breastfed their babies. All of these infants were exclusively breast-fed at discharge and growth of these infants was satisfactory at 3 months follow-up. Authors concluded that lactation failure following delayed initiation of breastfeeding can be countered by subsequent intensive counselling.

Mathur NB et al. Indian J pediatr 2009;76:1003-06

Gemfibrozil in Late Preterm and Term Neonates with Moderate Jaundice: A Randomized Controlled Trial
Authors hypothesize that Gemfibrozil, a safer sibling of Clofibrate, being an inducer of glucuronidation of bilirubin may decrease the duration of phototherapy in neonates with non-hemolytic jaundice. This double blind placebo controlled trial was carried out at tertiary care neonatal center in Northern India. Ninety seven term and late-preterm neonates requiring phototherapy during first seven days of age were given either two doses of Gemfibrozil (60 mg/kg/dose) or placebo, 12 hours apart. There was no significant difference in median duration of phototherapy or peak serum bilirubin levels between the two groups; however Gemfibrozil was not associated with any significant side effects.

JaiKrishan et al. Indian Pediatr 2009;46: 1063-1069.

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Pediatrics

Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children
This retrospective database analysis at Boston revealed, of all children below 7 years, during winter season, nearly 2.1% visited emergency department for RSV infection and 1% for influenza infection. Incidence of RSV infection was much higher for children below 2 years of age (6.4%).

Bourgeois FT et al. Pediatrics 2009; 124: e1072-e1080.
**Exact incidence of these viral illnesses in India is not known, but, I think it may be much higher compared to western countries because of overcrowding and poor sanitary habits; however, because of lack of rapid diagnostic tests and specific treatment these are usually underrated.

Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers
Based on observation that toddlers from unprivileged sector, accustomed to low dietary calcium intake but vitamin D replete have low serum ionised calcium and inappropriately raised serum inorganic phosphorus concentrations together with elevated serum parathyroid hormone (PTH) concentrations, authors hypothesised that dietary calcium deficiency leads to end organ resistance to PTH, thus resulting in mild hypocalcaemia and hyperphosphataemia, and that this would be reversed by oral calcium supplementation. This randomized placebo controlled trial of dietary calcium supplementation, enrolling 51 children from urban slum of Pune, reported significant increase in serum ionized calcium concentration, decrease in serum phosphorus concentration and mean serum PTH in calcium supplemented compared to placebo group. Calcium was supplemented in the dose of 500 mg, daily, for 8 weeks. From these data the authors concluded that low dietary calcium intake is associated with resistance to PTH.

Khadilkar A et al. Arch Dis Child 2009;94:932-937.

Blood pressure in children aged 4–8 years: comparison of Omron HEM 711 and sphygmomanometer blood pressure measurements
Midgley PC et al compared the blood pressure measurements by sphygmomanometer and a portable automated oscillometric BP monitor (Omron HEM 711 with child cuff) in healthy children between 4-8 y. Cross-sectional observational study including 764 children revealed lack of consistency between the two methods of BP measurement. With systolic BP there was a trend for the Omron to underestimate when low and overestimate when high. Authors concluded that with a wide variation between the two 5|Page

methods of BP measurement, comparison of automated BP measurements with normative data obtained by sphygmomanometer may not be valid.

Midgley PC et al. Arch Dis Child 2009;94:955-58.

Association of Tobacco and Lead Exposures with Attention-Deficit/Hyperactivity Disorder
In a cross-sectional study including 2588 children between 8 to 15 years of age, significantly higher risk of ADHD was found in child who had prenatal tobacco exposure (aOR 2.4; 95% CI 1.3 to 3.7) and higher current blood lead levels (aOR 2.3; 95% CI 1.5 to 3.8). Risk was much higher with combined exposure (prenatal tobacco exposure and high lead levels) (aOR 8.1; 95% CI 3.5 to 18.7).

Froehlich TE et al. Pediatrics 2009; 124: e1054-e1063.
**Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as insomnia, delirium, cognitive deficits, tremor, hallucinations, and convulsions. Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms. Some lead compounds are of bright colors and are widely used in paints. Deteriorating lead paint can produce dangerous lead levels in household dust and soil. Deteriorating lead paint and lead-containing household dust are the main causes of chronic lead poisoning in young children. Even a small amount of a lead-containing product such as a paint chip or a sip of glaze can contain tens or hundreds of milligrams of lead. Contaminated soil and water also contributes to lead exposure in urban areas. Now-a-days toys made in China are probably the most common source of chronic lead poisoning for children. Though, in 2007 millions of toys made in China were recalled from market of multiple countries due to safety hazards including lead paint (import bans initiated by the product safety institutions of the United States, Canada, the European Union, Australia and New Zealand against products manufactured in and exported from the mainland of the China), in India they are freely available due to low cost and unsupervised trade.

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How do current researches would change my practice?
We all know from our residency days that risk of adverse pregnancy outcome increase in subsequent pregnancies for several uterine, hormonal, pathogenic, or genetic factors. Recently published data by Svein et al supported this knowledge and suggested that even probably paternal genetic or idiopathic factors might play some part in it. Genital infections with human papillomaviruses (HPVs) are linked to approximately 99% of cervical cancer cases, one of the most common causes of death among Indian women. As organised

gynaecological screening programs with appropriate treatment of the detected pre-cancerous lesions is not feasible in current health care delivery system of India, vaccination against HPVs may be a great hope in the fight against cervical cancer. Two studies in current issue of Obstetrics & Gynecology journal have added to vast literature on safety & efficacy of vaccine against HPVs published in last few years. We already knew about some community based trials reporting efficacy of skin cleaning with chlorhexidine wipes for prevention of early onset neonatal sepsis; however, recent multicenter trial from the PoPS trial team did not supported the same. I will still wait for more data, before implementing regular use of these wipe in my unit. Recent trial from Israel refuted the common belief of increase in resting energy expenditure of the babies when breast feed compared to bottle feed. Now, probably, it will be easier for me to convince my nursing staff for early start of breast feed in preterm neonates. Moreover, I will reemphasize on intensive lactation counseling for perceived lactation failure. Finally, Froehlich et al again showed that chronic lead poisoning can present with any kind of symptoms. I strongly believe that in our country chronic lead poisoning is much more prevalent than what we thought of. And, cheaper and easily available Chinese toys are probably the most common source of chronic lead poisoning followed by bright colored local paints, mainly for our toddlers who try to explore everything from their mouth SM Correspondence:

Dr Satish Mishra
MD Pediatrics DM Neonatology (AIIMS, New Delhi)

Consultant Neonatologist & Pediatrician Narayan BabyCare Clinic E – 4/94, 10 No. Stop, Arera Colony, Bhopal – 462016 Phone: +91-755-2420042, Email: nbc.clinic@gmail.com
Disclaimer: Author has no commercial interest with the The NeoUpdates bulletin. This bulletin is solely for increasing academic discussion among young pediatricians & obstetricians.

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