Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

Pharmacology of milrinone in neonates with persistent pulmonary hypertension of the newborn and suboptimal response to inhaled nitric oxide.

OBJECTIVES: Persistent pulmonary hypertension of the newborn is a common problem with significant morbidity and mortality. Inhaled nitric oxide is the standard care, but up to 40% of neonates are nonresponders. Milrinone is a phosphodiesterase III inhibitor which increases the bioavailability of cyclic adenosine monophosphate and has been shown to improve pulmonary hemodynamics in animal experimental models. The primary objective was to investigate the pharmacological profile of milrinone in persistent pulmonary hypertension of the newborn. Secondary objectives were to delineate short-term outcomes and safety profile. SUBJECTS AND METHODS: An open label study of milrinone in neonates with persistent pulmonary hypertension of the newborn was conducted. Patients received an intravenous loading dose of milrinone (50 µg/kg) over 60 mins followed by a maintenance infusion (0.33-0.99 µg/kg/min) for 24-72 hrs. Physiologic indices of cardiorespiratory stability and details of cointerventions were recorded. Serial blood milrinone levels were collected after the bolus, following initiation of the maintenance infusion to determine steady state levels, and following discontinuation of the drug to determine clearance. Echocardiography was performed before and after (1, 12 hrs) milrinone initiation. INTERVENTIONS: Milrinone. MEASUREMENTS AND MAIN RESULTS: Eleven neonates with a diagnosis of persistent pulmonary hypertension of the newborn who met eligibility criteria were studied. The median (SD) gestational age and weight at birth were 39.2 ± 1.3 wks and 3481 ± 603 g. The mean (± sd) half-life, total body clearance, volume of distribution, and steady state concentration of milrinone were 4.1 ± 1.1 hrs, 0.11 ± 0.01 L/kg/hr, 0.56 ± 0.19 L/kg, and 290.9 ± 77.7 ng/mL. The initiation of milrinone led to an improvement in PaO2 (p = 0.002) and a sustained reduction in FIO2 (p < 0.001), oxygenation index (p < 0.001), mean airway pressure (p = 0.03), and inhaled nitric oxide dose (p < 0.001). Although a transient reduction in systolic arterial pressure (p < 0.001) was seen following the bolus, there was overall improvement in base deficit (p = 0.01) and plasma lactate (p = 0.04) with a trend towards lower inotrope score. Serial echocardiography revealed lower pulmonary artery pressure, improved right and left ventricular output, and reduced bidirectional or right-left shunting (p < 0.05) after milrinone treatment. CONCLUSIONS: The pharmacokinetics of milrinone in persistent pulmonary hypertension of the newborn is consistent with published data. The administration of intravenous milrinone led to better oxygenation and improvements in pulmonary and systemic hemodynamics in patients with suboptimal response to inhaled nitric oxide. These data support the need for a randomized controlled trial in neonates.

Use of targeted neonatal echocardiography to prevent postoperative cardiorespiratory instability after patent ductus arteriosus ligation.

OBJECTIVES: To investigate the value of targeted neonatal echocardiography (TnECHO) in predicting cardiorespiratory instability after patent ductus arteriosus (PDA) ligation, and to evaluate the impact of TnECHO-directed care. STUDY DESIGN: We reviewed serial echocardiography evaluations of 62 preterm infants after PDA ligation to investigate the relationship between indices of myocardial performance and postoperative cardiorespiratory instability. A predictive model was developed based on TnECHO criteria, with targeted initiation of intravenous milrinone. A comparative evaluation was performed between matched infants in the previous era (epoch 1; n=25) and current era (epoch 2; n=27) of TnECHO-guided treatment. RESULTS: Left ventricular output <200 mL/kg/min at 1 hour after PDA ligation was a sensitive predictor of systemic hypotension and the need for inotropes, and was used for initiation of i.v. milrinone infusion in epoch 2. Infants treated with milrinone had a lower incidence of ventilation failure (15% vs 48%; P=.02) and less need for inotropes (19% vs 56%; P=.01), and showed a trend toward improved oxygenation (P=.08). CONCLUSION: TnECHO facilitates early detection of infants at greatest risk for subsequent cardiorespiratory deterioration. Administration of milrinone to neonates with low cardiac output may lead to improved postoperative stability.

Validation of "Signs of Inflammation in Children that Kill" (SICK) score for immediate non-invasive assessment of severity of illness.

OBJECTIVE: To validate the SICK scoring system's ability to differentiate between individuals with higher and lower probabilities of death METHOD: We performed a one year two-centre prospective evaluation of all children aged between one month and 12 years referred to the Paediatric team at St Stephens Hospital in Delhi and admitted to the Paediatric Department at West Middlesex University Hospital in London. We calculated SICK scores at presentation and correlated them with subsequent in-hospital mortality. We used discrimination by areas under receiver operating characteristic (ROC) curves to measure performance. RESULTS: We prospectively evaluated 3895 children in Delhi and 1473 children in London. The areas under the ROC curves were 84.8% in Delhi, 81.0% in London and 84.1% (95% CI 77.4-90.8%) for combined data. Hosmer-Lemeshow goodness of fit for the combined data was good (Hosmer-Lemeshow Chi-square=2.13 (p=0.345). CONCLUSIONS: We propose the SICK score as a useful triage tool at initial presentation and highlight its particular suitability for resource poor settings.

Missing girls in India: infanticide, feticide and made-to-order pregnancies? Insights from hospital-based sex-ratio-at-birth over the last century.

BACKGROUND: There are 44 million missing women in India. Gender bias; neglect of girls, infanticides and feticides are responsible. The sex ratio at birth can be used to examine the influence of antenatal sex selection on the sex ratio. MATERIALS AND METHODS: Records from 321,991 deliveries at one hospital over 11 decades were utilized. The middle year in each decade was taken as representative of the decade. Data from 33,524 deliveries were then analyzed. Data for each decade was combined with that of previous decades and compared to the data of subsequent decades to look for any change in the trend. Sex ratio in the second children against sex of the first child was studied separately. RESULTS: The mean sex ratio for the 110 years examined was 910 girls to 1000 boys (95% CI; 891 to 930). The sex ratio dropped significantly from 935 (CI: 905 to 967) before 1979, to 892 (CI: 868 to 918) after 1980 (P = 0.04). The sex ratio in the second child was significantly lower if the first child was a girl [716 (CI: 672 to 762] (P<0.001). On the other hand, there was an excess of girls born to mothers whose first child was boy [1140 girls per 1000 boys (CI: 1072 to 1212 P<0.001)]. CONCLUSIONS: The sex ratio fell significantly after 1980 when ultra sound machines for antenatal sex determination became available. The sex ratio in second children if the first was a girl was even lower. Sex selective abortions after antenatal sex determination are thus implicated. However data on second children especially the excess of girls born to mothers who have a previous boy seen in the decade before the advent of antenatal ultra sound machines, suggests that other means of sex selection are also used.

Swan-neck sign of the big toe - association with hypocalcaemia.

The sensitivity and specificity of a new clinical sign of hypocalcaemia were evaluated. The Swan-neck sign, wherein infants with symptomatic hypocalcaemia keep their big toe hyperextended at the metatarsophalangeal joint and flexed at the interphalangeal joint, was looked for in 25 infants presenting with non-febrile seizures, alongside their serum calcium levels. The study showed that the sign had a sensitivity of 63.6% and specificity of 66.6%. (Predictive values of positive and negative tests were 93.3% and 20%, respectively.) This is compared with the standard Trousseau and Chvostek signs.

Outbreak of Coxsackie B4 arthritis among newborns and staff of a neonatal unit.

We investigated an outbreak of Coxsackie B4 arthritis in a neonatal unit involving 20 neonates and 12 staff members, over an eight-month period. Laboratory investigations, serology tests, indicate that the outbreak was caused by Coxsackie B4 virus. Contamination of one of the overhead water reservoirs, supplying the nursery, was responsible. After the water tanks were cleaned out, no new cases were reported over five years.

Discordant twins with the smaller baby appropriate for gestational age--unusual manifestation of superfoetation: a case report.

BACKGROUND: Documentation of superfoetation is extremely rare in humans., The younger foetus has invariably been small for gestational age (estimated from the date of the last menstrual bleed) in all the cases reported in the literature. We report a case where the younger twin was of appropriate size for gestation. CASE PRESENTATION: The first of twins was of 32 weeks gestation and the baby was of appropriate size and development for the gestational age. The second twin was of 36 weeks gestation. Gestational age was estimated with the New Ballard score, x-ray of the lower limbs, dental age on x-ray, and ophthalmic examination. CONCLUSION: Bleeding on implantation of the first foetus probably helped demarcate the two pregnancies. Dental age and the New Ballard score can be used to diagnose superfoetation in discordant twins, when detailed first trimester ultra-sound data is not available.

Tracheal agenesis: two case reports.

Tracheal agenesis is a rare and uniformly lethal congenital malformation. It presents with severe respiratory distress at birth. In this anomaly there is a congenital absence of the trachea and the bronchus communicates with the esophagus. The diagnosis should be suspected in newborn infant with respiratory distress whose intubation is impossible. This report describes our experience in two such cases.

Congenital pouch colon with prune belly syndrome and megalourethra.

Congenital pouch colon (CPC), an unusual high anorectal malformation in which a varying length of colon is replaced by a dilated pouch, has appeared in a number of case reports and series published in the English literature. There is only one case report of its association with prune belly syndrome (also known as triad syndrome, Eagle-Barrett syndrome, and abdominal muscle deficiency syndrome). We report the description and management of this rare association in a male neonate with CPC, prune belly syndrome, and congenital megalourethra.

Hepatitis B immunization: cost calculation in a community-based study in India.

BACKGROUND AND AIM: In India, approximately 65% of mothers deliver at home, and a community-based study evaluating the cost of vaccinating newborns with the first dose of hepatitis B vaccine within 48 hours has not been undertaken previously. This policy planning study was done to evaluate the costs of such immunization in India. METHODS: All mothers delivering in the study area (population 65,000) over a 1-year period were tested for hepatitis B surface antigen (HBsAg; ELISA), and babies of positive mothers were vaccinated starting at birth. The cost of such selective vaccination was calculated. The cost of nursing time required for universal immunization was calculated from the data on nursing time required for vaccination in the selective vaccination program. The national cost of universal immunization without testing was calculated as well as cost-benefit and cost-utility in terms of cost per quality-adjusted life-year (QALY) saved. Sensitivity testing considering economies of scale was also factored in. RESULTS: 1100 mothers delivered during the study period. 252 were primiparous. Nationwide universal vaccination would cost Rs 48,000 per QALY saved, which was double the per capita GNP of the country; discounted at 3% the cost was Rs 260,000. CONCLUSIONS: Universal immunization vaccination with hepatitis B vaccine is not cost-beneficial in India, since cost of every life-year gained with it will exceed India's per capita GNP.