John C. Sinclair

Temperature Regulation in the Newborn Infant

MAN thrived earliest and most prolifically in areas of the world with a mean annual temperature close to 21°C. (70°F.).1 His migrations from the 21°C. isotherm were for the most part associated wit...

Clinically useful measures of effect in binary analyses of randomized trials

The results of a randomized clinical trial can be reported using relative and/or absolute estimators of treatment effect. These various measures convey different information, and the choice can influence the physicians appreciation of the size of treatment effect and, subsequently, treatment decisions. We compare the estimators with respect to the clinically relevant information conveyed to physicians, and identify which clinical questions can and cannot be answered directly by each. We also identify opportunities for misinterpretation when one estimator is substituted for another, or when an estimator is mislabeled. Clinically important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement, relative risk reduction, and risk difference and its reciprocal, number needed to treat. This is true of estimates of treatment effect derived from a single trial and also from meta-analysis of a group of trials. Because the control groups risk affects the numerical value of the odds ratio, the odds ratio cannot substitute for the risk ratio in conveying clinically important information to physicians. This is especially important when large treatment effects are shown in trials carried out in populations at high baseline risk.

Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk for Chronic Lung Disease

Objective. In preterm infants, chronic lung disease (CLD) is associated with an increased risk for cerebral palsy (CP). However, systemic postnatal corticosteroid therapy to prevent or treat CLD, although effective in improving lung function, may cause CP. The objective of this study was to determine the effect of systemic postnatal corticosteroid treatment on death and CP and to assess any modification of effect arising from risk for CLD. Methods. Randomized, controlled trials of postnatal corticosteroid therapy for prevention or treatment of CLD in preterm infants that reported rates of both mortality and CP were reviewed and their data were synthesized. Twenty studies with data on 1721 randomized infants met eligibility criteria. The relationship between the corticosteroid effect on the combined outcome, death or CP, and the risk for CLD in control groups was analyzed by weighted meta-regression. Results. Among all infants who were randomized, a significantly higher rate of CP after corticosteroid treatment (typical risk difference [RD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08) was partly offset by a nonsignificant reduction in mortality (typical RD: −0.02; 95% CI: −0.06 to 0.02). Consequently, there was no significant effect of corticosteroid treatment on the combined rate of mortality or CP (typical RD: 0.03; 95% CI: −0.01 to 0.08). However, on meta-regression, there was a significant negative relationship between the treatment effect on death or CP and the risk for CLD in control groups. With risks for CLD below 35%, corticosteroid treatment significantly increased the chance of death or CP, whereas with risks for CLD exceeding 65%, it reduced this chance. Conclusions. The effect of postnatal corticosteroids on the combined outcome of death or CP varies with the level of risk for CLD.

Evaluation of Neonatal-Intensive-Care Programs

Within the past 15 years, regional neonatal-intensive-care programs have been introduced and have expanded rapidly. The efficacy of some of the individual interventions that constitute neonatal intensive care has been validated in randomized, controlled clinical trials. It is therefore generally assumed that neonatal-intensive-care programs that incorporate these maneuvers are effective in reducing death and disability. However, the overall effectiveness of these programs has not been tested experimentally. Moreover, much of the non-experimental evidence supporting their value is based on the experience of referral units and does not measure the impact on the populations they serve. A definitive economic evaluation of neonatal intensive care has not yet been reported, despite the high cost of such programs. We conclude that neonatal-intensive care programs require further evaluation with rigorous scientific methods.

Outcome in infants 501 to 1000 gm birth weight delivered to residents of the McMaster Health Region.

The mortality and morbidity for all 255 live births of infants with birth weight 501 to 1000 gm and delivered to residents of a geographically defined region between 1977 and 1980 are reported. In all, 117 (46%) infants were discharged alive; there were four postdischarge deaths, and three infants were lost to follow-up. The mean birth weight and gestational age of the survivors was 850 +/- 118 gm and 27.1 +/- 2 weeks, respectively. Neurosensory handicaps were detected in 26 (24%) of 110 survivors followed for a minimum of 2 years corrected age. In addition, 29 (26%) infants had nonneurologic problems and 55 (50%) were considered apparently normal. Within 100 gm birth weight groups, survival improved significantly with increasing birth weight, but the handicap rate among survivors remained relatively constant. These figures are proposed for use in describing the current prognosis at birth for liveborn tiny infants from comparable unselected populations.

Determinants of size at birth in a Canadian population.

Anthropometric, medical, and sociodemographic characteristics and smoking habit of a random sample of postpartum women in a Canadian population were determined. These characteristics were analyzed in relation to the birth size of their babies. With controls for gestational age and fetal sex, the following maternal variables were positively correlated with birth weight: prepregnant weight, weight gain in pregnancy, stature, bicristal and biacromial diameter, calf and upper arm circumference, and triceps and subscapular skinfold thickness. Smoking during pregnancy reduced birth weight by 13 gm per cigarette smoked daily. Similar associations of maternal size and smoking habit were observed with respect to infant length, head circumference, and chest circumference. The predictors of birth weight are proposed for use in adjusting upward or downward the population distribution of birth weight to reflect the individual characteristics of the mother.

Meta-analysis of randomized controlled trials of antenatal corticosteroid for the prevention of respiratory distress syndrome: Discussion

different approaches to the prevention of respiratory distress syndrome. Arch Dis Child 1991;66:757-64. 76. Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990;97: 1 l-25. 77. Garite TJ, Freeman RK, Linzey EM, Braly PS, Dorchester WL. Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation. AM J OBSTET GYNECOL 1981; 141:508-15. 78. Iams JD, Talbert ML, Barrows H, Sachs L. Management of prematurely ruptured membranes: a prospective randomized comparison of observation versus steroids and timed delivery. AM J OBSTET GYNECOL 1985;151:32-8. 79. Nelson LH, Meis PJ, Hatjis CG, Ernest JM, Dillard R, Schey HM. Premature rupture of membranes; a prospective, randomized evaluation of steroids, latent phase and expectant management. Obstet Gynecol 1985;66:55-8. 80. Farrag OAM. Prospective study of three metabolic regimensin pregnant diabetics. At27:6-9. 81. Keirse MJNC, Kanhai HHH. An obstetrical viewpoint on preterm birth with particular reference to perinatal mortality and morbidity. In: Huisjes HJ, ed. Aspects of perinatal morbidity. Groningen: Universitaire Boekhandel Nederaland, 1981:1-35. 82. Tubman TRJ, Rollins MD, Patterson C, Halliday HL. Increased incidence of respiratory distress syndrome in babies of hypertensive mothers. Arch Dis Child 1991;66: 52-4. 83. Lamont RF, Dunlop PDM, Levene MI, Elder MI. Use of glucocorticoids in pregnancies complicated by severe hypertension and proteinuria. Br J Obstet Gynaecol 1983; 90:199-202. 84. Farrell PM, Engle MJ, Zachman RD, et al., and the Collaborative Group on Antenatal Steroid Therapy. Amniotic fluid phospholipids after maternal administration of dexamethasone. AV J OSSTET GYNECOL 1983;145:484-90.

Energy balance and nitrogen balance in growing low birthweight infants fed human milk or formula

Summary: Energy and nitrogen balances were measured in growing low birthweight infants fed either mothers expressed breast milk or a 20 kcal per ounce formula to determine whether or not there were differences between the two dietary groups in (1) the partition of energy among excretion, expenditure, and storage and (2) the relation of energy storage and nitrogen retention to weight gain.There were no significant differences between the human milk fed infants and formula fed infants in gross energy intake, metabolizable energy intake, nitrogen intake, or nitrogen retention. Energy expenditure was significantly lower in the human milk fed infants than in formula fed infants (221 kJ/(kg. day) and 244 kJ/(kg. day), respectively). There was no difference in mean energy storage between the two groups.Although weight gains were similar in both dietary groups, the ratio of energy storage to weight gain was significantly greater in infants fed with human milk (15.3 kJ/g, S.D. 2.0) than in infants fed formula (13.2 kJ/g S.D. 1.8). There was no significant difference between the two groups in the ratio of nitrogen stored to weight gain.

An Update on the Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk of Bronchopulmonary Dysplasia

Infants at higher risk of bronchopulmonary dysplasia had increased rates of survival free of cerebral palsy after postnatal corticosteroid treatment in a previous metaregression of data from 14 randomized controlled trials. The relationship persists and is stronger in an updated analysis with data from 20 randomized controlled trials.

Diurnal variation in the quality and outcome of newborn intensive care

Variables related to both the process and the outcome of neonatal intensive care were studied to compare care given during the day (0901-2100 hours) with that at night (2101-0900 hours). At night, intravenous infiltrations occurred more often, and the tidal volume of respirator-treated infants was verified less often. Blood pH values less than 7.20, excluding values within 12 hours of admission, were recorded more often and in more patients at night. During a 12-month period, there were significantly more deaths among infants less than 1,500 gm during the night than during the day. The deterioration of infants at night may result in part from current nursery staffing practices.