Srinivas Bolisetty

Intraventricular Hemorrhage and Neurodevelopmental Outcomes in Extreme Preterm Infants

OBJECTIVE: Not many large studies have reported the true impact of lower-grade intraventricular hemorrhages in preterm infants. We studied the neurodevelopmental outcomes of extremely preterm infants in relation to the severity of intraventricular hemorrhage. METHODS: A regional cohort study of infants born at 23 to 28 weeks’ gestation and admitted to a NICU between 1998 and 2004. Primary outcome measure was moderate to severe neurosensory impairment at 2 to 3 years’ corrected age defined as developmental delay (developmental quotient >2 SD below the mean), cerebral palsy, bilateral deafness, or bilateral blindness. RESULTS: Of the 1472 survivors assessed, infants with grade III–IV intraventricular hemorrhage (IVH; n = 93) had higher rates of developmental delay (17.5%), cerebral palsy (30%), deafness (8.6%), and blindness (2.2%). Grade I–II IVH infants (n = 336) also had increased rates of neurosensory impairment (22% vs 12.1%), developmental delay (7.8% vs 3.4%), cerebral palsy (10.4% vs 6.5%), and deafness (6.0% vs 2.3%) compared with the no IVH group (n = 1043). After exclusion of 40 infants with late ultrasound findings (periventricular leukomalacia, porencephaly, ventricular enlargement), isolated grade I–II IVH (n = 296) had increased rates of moderate-severe neurosensory impairment (18.6% vs 12.1%). Isolated grade I–II IVH was also independently associated with a higher risk of neurosensory impairment (adjusted odds ratio 1.73, 95% confidence interval 1.22–2.46). CONCLUSIONS: Grade I–II IVH, even with no documented white matter injury or other late ultrasound abnormalities, is associated with adverse neurodevelopmental outcomes in extremely preterm infants.

A regional study of underlying congenital diseases in term neonates with necrotizing enterocolitis.

Aim of the study: The aetiology of necrotizing enterocolitis (NEC) remains poorly understood in infants of all gestation, particularly when it occurs at term. We hypothesize that NEC in term infants is rare but often associated with underlying congenital illnesses. Method: Records of all term infants hospitalized with radiologically or surgically proven NEC in the 10 tertiary centres of two geographical regions of Australia during a 6.5‐y period were reviewed. Regional birth data were obtained and a special care nursery survey was conducted. Results: Twenty‐nine infants had proven NEC giving a population incidence of 0.05 per 1000 live births. Nineteen (66%) of them had underlying congenital diseases. Five (17%) infants had endocrine disorders, which included panhypopituitarism, hypothyroidism, hypoparathyroidism and congenital adrenal hyperplasia. Ten infants had congenital heart disease, eight being cyanotic. Six of them developed NEC prior to any invasive cardiac procedures. Seven of the other nine infants without any congenital diseases had perinatal risk factors associated with NEC. The severity of illness was not different amongst the three groups. All infants, except two, survived.

Randomised controlled trial of cisapride in feed intolerance in preterm infants

AIM To assess the efficacy of cisapride in reducing the time required to establish enteral feeds in preterm infants. METHODS A randomised, double blind, placebo controlled trial was conducted of 34 infants of ⩽ 32 weeks of gestation, assigned to receive either cisapride 0.2 mg/kg/dose four times daily (n=18) or placebo (n=16). RESULTS The time taken by the babies to tolerate full enteral feeds was not significantly different between the groups (median 9.5 days vs 10 days). There was a significantly lower incidence of large gastric residuals and regurgitation in the treated group compared with the placebo group. The number of episodes of large gastric residuals per infant was also significantly less. No adverse effects were noted. CONCLUSION The routine use of cisapride in preterm infants cannot be recommended to decrease the time to establish enteral feeds. Its use may be justified for clincally significant gastric stasis or regurgitation.

Preterm outcome table (POT): a simple tool to aid counselling parents of very preterm infants.

Background:  Outcome figures published in scientific journals are often cumbersome and difficult to understand by parents during counselling before or immediately after a very premature birth.

Postnatal changes in maternal and neonatal plasma antioxidant vitamins and the influence of smoking

Objective: To study the postnatal changes in the plasma concentrations of fat soluble antioxidant vitamins and malondialdehyde (MDA) in mothers and their newborns and their relation to smoking. Design: Prospective cohort study. Setting: Tertiary perinatal centre. Subjects: Eighteen non-smoking and 14 smoking mothers and 33 infants. Main outcome measures: Plasma concentrations of vitamins E, A, and β-carotene and MDA were measured in mothers and infants at delivery and on day 4 post partum. Results: Neonatal plasma levels of vitamins E, A, and β-carotene were significantly lower than maternal levels both at delivery and on day 4 in both groups. There was a significant postnatal increase in plasma vitamin E levels in smoking mothers and neonates of both groups. A significant postnatal increase in maternal, but not neonatal, plasma vitamin A was noted in both groups. Cord plasma vitamin E levels were significantly lower in infants of smoking mothers (mean 4.7 v 6.5 μmol/l, p = 0.041). Plasma MDA was paradoxically lower in smoking mothers at delivery (3.19 v 4.01 μmol/l, p = 0.03) and on day 4 (1.37 v 3.29 μmol/l , p = 0.005) and in infants of the smoking group on day 4 (2.18 v 3.12 μmol/l, p = 0.014). Also, there was a significant postnatal fall in plasma MDA levels on day 4 in mothers and infants in the smoking group. Conclusions: The postnatal changes in plasma vitamin E were more pronounced in the smoking group. The postnatal changes in plasma vitamins A and β-carotene were similar in both groups. The rapid decline in plasma MDA in smoking mothers and their infants suggests withdrawal of oxidative stress from smoking around delivery. This coincided with the increase in plasma vitamin E.

Mode of delivery and neonatal survival of infants with gastroschisis in Australia and New Zealand.

OBJECTIVE The aim of the study was to examine the short-term outcome of infants with gastroschisis by route of delivery, comparing vaginal delivery vs elective and emergency cesarean delivery (CD). METHODS Six hundred thirty-one infants with gastroschisis (International Classification of Diseases, 10th Revision: Q79.3) were admitted to the Australian and New Zealand Neonatal Network during 1997 to 2005. Multivariate Cox proportional hazards regression analysis was performed to adjust for case-mix and significant baseline characteristics. RESULTS During the study period, 631 infants with gastroschisis were admitted to the collaborating centers. Of these, 343 (54.4%) infants were delivered vaginally, whereas 288 (45.6%) were delivered by cesarean birth. Of the latter, 148 (23.4%) were elective and 140 (22.2%) were emergency. There was an increasing trend of CD from 41.1% in 1997 to 69.0% in 2005. Forty-seven (7.4%) infants died; 30 (8.7%) in the vaginal, 9 (6.4%) in the emergency, and 8 (5.4%) in the elective CD group. There was no difference in rate of proven infection, duration of ventilation, or length of neonatal intensive care unit stay between the 3 groups. After controlling for prematurity, low birth weight, and outborn birth, the risk for neonatal demise was similar in both the vaginal and CD infants (adjusted hazard ratio, 1.486; 95% confidence interval, 0.814-2.713; P = .197). Stratifying the CD (emergency vs elective) gave similar results. CONCLUSION Infants with gastroschisis appear to be safely delivered vaginally.

Perinatal characteristics and outcome of preterm singleton, twin and triplet infants in NSW and the ACT, Australia (1994-2005)

Objective: To compare the perinatal characteristics, neonatal morbidity and mortality of preterm singletons, twins and triplets born at 22–31 weeks’ gestation and admitted to neonatal intensive care units (NICU) in New South Wales and Australian Capital Territory between 1994 and 2005. Methods: Perinatal characteristics and neonatal outcome data were obtained from the regional NICUS data collection to test for a priori hypothesis. The 10 068 very premature infants studied included 7304 (72.5%) singletons, 2444 (24.2%) twins and 320 (3.2%) triplets. Results: Assisted conception was associated with a higher maternal age and increased twins and triplets admissions into NICU than spontaneous conceptions (twins OR 6.9, 95% CI 6.1 to 8.0; and triplets OR 35.6, 95% CI 27.6 to 45.8). Major neonatal morbidities were similar between the three groups of singletons, twins or triplets. While twins of 22–27 weeks’ gestation (adjusted OR 1.39, 95% CI 1.12to 1.72) had higher mortality compared with singletons, mortality only diverged below 24 weeks’ gestation. Mortality was predicted by decreasing gestational age, male gender and lack of antenatal steroids, whereas assisted conception was protective against mortality (adjusted OR 0.69, 95% CI 0.57 to 0.86). Conclusions: Assisted conception contributed to higher very premature NICU admissions of twins and triplets. Preterm twins at the very extreme of viability had higher mortality compared with singletons. The protective effect of assisted conception against mortality requires further research.

Antenatal supplementation of antioxidant vitamins to reduce the oxidative stress at delivery: a pilot study

BACKGROUND Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state. The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants. STUDY DESIGN A pilot case-control study. PATIENTS AND METHODS Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg, vitamin E 167.8 mg and vitamin C 1000 mg until delivery. Plasma levels of MDA and vitamins A, E and beta-carotene were measured prior to treatment in mothers and at delivery in both mothers and neonates. Seven mother-infant pairs comparable in gestation and birthweight acted as controls. RESULTS In the supplemented group, median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level (1.9 vs. 3.2 micromol/l, p=0.04) and it was also lower than the control group (1.9 vs. 3.65 micromol/l, p<0.001). In the supplemented group, median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment (46 vs. 31 micromol/l, p=0.007) in the same group and those at delivery in the control group (46 vs. 30 micromol/l, p=0.03). There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers, but it did not reach statistical significance. CONCLUSION A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates. Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy.

Neonatal seizures from in utero venlafaxine exposure

Abstract:  Venlafaxine (Efexor), a selective noradrenergic reuptake inhibitor, is an important therapeutic option in the treatment of perinatal depression, but its effects on the newborn are uncertain. We present a report of two infants with neonatal seizures attributed to maternal use of venlafaxine. The first infant was hypotonic and required resuscitation at birth. The second was born in a good condition but developed clinically apparent seizures after the second day of life. Both infants responded rapidly to treatment with phenobarbitone that was weaned uneventfully by the first and second week of life. Both remain well at 1 year of age. Other causes of neonatal seizures were excluded and neurological investigations on these two infants were unremarkable. We suggest that all infants exposed to maternal venlafaxine, no matter their condition at birth, be monitored in hospital for at least 3 to 4 days in order to pre‐empt and treat adverse neurological events.

Vitamin K in preterm breastmilk with maternal supplementation

Six healthy lactating mothers who gave birth to preterm infants at a median post conceptional age of 29.5 (range 26‐30) weeks were given 2.5 mg phylloquinone (vitamin K1) orally daily for 2 weeks beginning at a median postconceptional age of 31.5 (range 28–32) weeks. Phylloquinone was measured in the breastmilk daily for 14 d. Trough plasma phylloquinone concentrations were also determined on four occasions. Phylloquinone levels in the breastmilk increased from a baseline of 3 ± 2.3ngml‐1 to 22.6 ± 16.3 ng ml‐1 (mean ± SD) after the first dose (p < 0:05); a gradual increase was noted until phylloquinone levels reached a plateau of 64.2 ± 31.4ng ml‐1 after the sixth daily dose.