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• We investigated the contribution of brain growth failure to outcome in infants of very low birth weight (VLBW; <1.5 kg) who were appropriate for gestational age (AGA; n = 379) or small for gestational age (SGA; n=102). Growth was assessed at birth, term, and 8 and 20 months' corrected age and results of a Bayley Mental Developmental Index (MDI) and neurologic examination were evaluated at 20 months of age. Both groups had similar 20-month MDI scores (93 vs 90) and similar rates of neurologic impairment (14% vs 10%). More SGA infants (25%) than AGA infants (14%) had a subnormal head circumference at 8 months' corrected age, indicating failure to catch up in head growth. Subnormal head size at 8 months predicted the 20-month MDI score for both groups. However, multivariate analysis indicated that, whereas subnormal 8-month head size was directly associated with the MDI score in AGA children, in SGA children 8-month head size was not significantly related to the MDI score when neonatal illness, neurologic impairment, socioeconomic status, and race were controlled for. We conclude that in AGA VLBW infants, subnormal head size at 8 months results from major neonatal illness and has adverse later effects. In SGA infants, subnormal head size at 8 months has many causes, including growth retardation in utero, which may not have an adverse effect on outcome; if subnormal head size is superimposed with neonatal illness, a poorer outcome is likely.(AJDC 1989;143:63-68)

• There is little information concerning long-term outcome of vertebral agenesis. In this series of eight patients with variable severity of vertebral agenesis, three died during infancy, two of associated congenital anomalies involving the cardiorespiratory system and one of unknown causes. The remaining five have had no life-threatening problems. They have normal intellect, and the developmental achievements are adequate for their age. The five patients with the highest lesions were those born to diabetic mothers. We also discuss current concepts of comprehensive team management of such infants.(Am J Dis Child 1982;136:533-537)

Summary: Baseline rates for secretion of mucous glycoprotein were similar (680–830 µg/g tissue/24 hr) for cultured tracheal epithelium from new horns of 26–32 weeks' gestation, full term newborns, and older children. Addition of methacholine to culture medium augmented secretory rates of glycoprotein from all tissue sources 3–5-fold. The overall composition of secreted mucous glycoproteins changed little with increasing age. A trend toward less sulfation and toward increased sialic acid and fucose content was noted in secreted glycoproteins from explants of older subjects. Histochemical observations of stored glycoprotein in tracheal tissue, which was subsequently used for organ culture experiments, confirmed that a modest, but consistent sulfate to sialic acid shift occurs during early life. In contrast, baseline secretory rates for lysozyme from tracheal epithelium of preterm infants were one-half as large as rates from epithelium of full term babies and were refractory to cholinergic stimulation. Stimulation of lysozyme secretion by a cholinergic agonist was achieved in all cases by 40 weeks' gestation. We conclude that basal glycoprotein secretion and the mechanism for glycoprotein response to cholinergic stimulation have developed by the earliest age of viability, but that basal lysozyme secretion is deficient and is unresponsive to cholinergic stimulation in tracheal tissue from preterm newborns.Speculation: The lungs of preterm inants may be more susceptable to bactrial invasion than lungs of full term infants and older children as a result of deficient lysozyme secretion by tracheobronchial epithelium.

To examine the relative importance of intrauterine growth failure, extrauterine growth failure before or after term, and the prognostic significance of catch-up growth, 192 very low-birth weight infants (< 1.5 kg) were followed prospectively to 8 months corrected age. One hundred fifty-four appropriate-for-gestational age (AGA) and 38 small-for-gestational age (SGA) infants were categorized into normal and subnormal (< −2 SD) weight for age groups at term (40 weeks) and at 8 months corrected age. By term, 71 AGA infants had subnormal weight; 41 of these caught up by 8 months, and an additional 13 AGA infants failed to thrive between term and 8 months. Of the SGA infants, three caught up in weight by term, and an additional 16 caught up by 8 months. Significant correlates of subnormal weight included neonatal risk score, incidence of chronic disease, and extended hospitalization. The AGA and SGA infants who failed to thrive or failed to catch up in weight by 8 months had lower mean Bayley developmental quotients (p < 0.005), smaller head circumferences (p < 0.005), and a higher rate of neurosensory impairment (p < 0.01) than the AGA infants with normal fetal and postnatal growth. Intrauterine and/or postnatal growth failure prior to term was not of sinister prognostic significance if catch up occurred thereafter.

We compared the extrauterine adaptation of preterm with term newborn infants, by sequentially measuring plasma catecholamine (CAT) levels at birth and during the first 24 h of life. Twenty-seven preterm appropriate-for-gestational-age (AGA) infants, less than 35 weeks gestation, were compared with 26 healthy near-term AGA infants. Modes of delivery and umbilical arterial pH (mean 7.28) did not differ. Infants with asphyxia, presumed sepsis or hypoglycemia were excluded. CAT (norepinephrine, epinephrine, dopamine) levels were measured by radioenzymatic assay in blood samples from maternal vein, cord vein, cord artery and blood samples obtained at 1, 2 and 24 h of postnatal age. At birth, the cord arterial CAT levels were significantly higher than maternal venous CAT levels in both groups of neonates. Plasma epinephrine levels (mean ± SD) at 1 and 2 h of postnatal age were significantly higher in preterm than in near-term newborns (0.98 ± 0.82 nmol/l vs. 0.30 ± 0.21 nmol/l at 1 h; 0.98 ± 0.68 nmol/l vs. 0.28 ± 0.29 nmol/l at 2 h; p < 0.05). The norepinephrine and dopamine measurements did not differ between the two groups studied at birth, 1, 2 and 24 h of postnatal age. These data indicate that the preterm infants (25-35 weeks gestation) are capable of mounting a catecholamine response at birth similar to near-term newborns. The persistent elevation of epinephrine in preterm infants at 1 and 2 h of life may be attributed to either slower clearance of epinephrine or continued stimulation during clinical care in the NICU.

Increased understanding of maternal-fetal carbohydrate homeostasis together with modern perinatal technology now provides a more rational basis for obstetric management of the pregnant diabetic patient. These concepts were applied at MacDonald House in the care of 96 diabetic pregnant women over a two-year period. Pregnancy outcomes were compared with prior experiences with the same group of women. The perinatal mortality rate was reduced from 13.5 to 4.2 per cent, and the rate of macrosomia (infants large for gestational age) was reduced from 30.9 to 17.7 per cent. Patients with gestational diabetes, with a prior loss rate of 8.3 per cent, suffered no losses in the current series. Maternal age was not found to correlate with an untoward outcome in this subgroup.

• Clinical correlates of catch-up growth were documented in 182 very-low-birth-weight (VLBW) infants (&lt;1.5 kg) followed up prospectively until a corrected age of 33 months. At birth, 147 infants had weights appropriate for gestational age (AGA), and 35 were small for gestational age (SGA). The infants in each group were categorized as small if body weight was 2 SDs below the mean for age or appropriate if body weight was within 2 SDs of the mean at birth and at corrected ages of 40 weeks and 8,21, and 33 months. Of the 147 AGA infants, 67 (46%) weighed less than 2 SDs of the mean for age at a corrected age of 40 weeks, 40 (27%) at 8 months, 28 (19%) at 21 months, and 25 (17%) at 33 months. Of the 35 SGA infants, 32 (91%) had subnormal weight at 40 weeks, 17 (49%) at 8 months and 21 months, and 16 (46%) at 33 months. Significant correlates of poor catch-up growth in the AGA group were birth weight, gestational age, severity of neonatal complications, poor neonatal head growth, and chronic physical and neurologic sequelae. In the infants in the SGA group, the correlates of poor catch-up growth were birth weight, multiple birth, and social class.(AJDC 1984;138:370-375)

• Mortality was assessed in a nine-year experience with 123 patients with necrotizing enterocolitis. Overall mortality was 45%. Despite intestinal perforation among surgically treated patients, there was no difference in mortality between surgically or medically treated patients (46% vs 54%). Patients with only hematochezia or abdominal distention had a lower mortality than those who appeared "septic" (35% vs 68%). Similarly, those with bacteremia and disseminated intravascular coagulation had high mortality as well as those in whom peritonitis with ascites developed. When the entire patient population is considered, prior therapy with systemic antibiotics or concomitant therapy with oral aminoglycosides had no effect on severity of the disease, occurrence of intestinal perforation, or mortality.(Am J Dis Child 1981;135:608-611)

• To gain an epidemiologic perspective on necrotizing enterocolitis (NEC), nine years' experience with 123 patients was reviewed. Mean gestational age was 31 weeks, and mean birth weight, 1,460 g; 7.3% were full-term and 10.5% were small for gestational age. Eighty infants had umbilical artery catheters, of which 50% were placed below L4-5. There was no identifiable risk factor in 11.4%; in half of these infants, NEC developed during an epidemic. Clustering of cases occurred in seven of the 108 months studied. Cases during epidemics had a lower incidence of respiratory distress syndrome. Average age at onset of NEC was 12 days; however the most common age (mode) was 3 days, and in 13.8% onset was after the third week. Of the survivors, 4% had recurrent disease one to 20 days after reinitiation of enteric feeding. The occurrence of NEC in low-risk patients and in older neonates raises serious questions about the proposed pathogenesis of NEC.(Am J Dis Child 1981;135:603-607)

• To evaluate ongoing morbidity, a prospective follow-up study was undertaken of the frequency and causes of rehospitalization of very-low-birth-weight infants (&lt;1,500 g) during the first year of life. In 1977, 90 very-low-birth-weight infants were discharged after an average of 62 days' hospitalization. Thirty required rehospitalization on 51 occasions during the first year, for reasons including continuing care of chronic conditions related to the initial neonatal hospitalization (16), respiratory and other infections (14), inguinal herniorrhaphy (13), caretaking disorders (five), and other causes (three). Infants at highest risk for rehospitalization included those with chronic conditions and/or those with poor neurodevelopmental outcomes. These data reconfirm the continuing toll of perinatal morbidity among very-low-birth-weight infants and emphasize the medical and social responsibility for a systematic program of follow-up for these high-risk infants.(Am J Dis Child 1981;135:263-266)

Baseline rates for secretion of mucous glycoprotein were similar (680–830 μg/g tissue/24 hr) for cultured tracheal epithelium from new horns of 26–32 weeks' gestation, full term newborns, and older children. Addition of methacholine to culture medium augmented secretory rates of glycoprotein from all tissue sources 3–5-fold. The overall composition of secreted mucous glycoproteins changed little with increasing age. A trend toward less sulfation and toward increased sialic acid and fucose content was noted in secreted glycoproteins from explants of older subjects. Histochemical observations of stored glycoprotein in tracheal tissue, which was subsequently used for organ culture experiments, confirmed that a modest, but consistent sulfate to sialic acid shift occurs during early life. In contrast, baseline secretory rates for lysozyme from tracheal epithelium of preterm infants were one-half as large as rates from epithelium of full term babies and were refractory to cholinergic stimulation. Stimulation of lysozyme secretion by a cholinergic agonist was achieved in all cases by 40 weeks' gestation. We conclude that basal glycoprotein secretion and the mechanism for glycoprotein response to cholinergic stimulation have developed by the earliest age of viability, but that basal lysozyme secretion is deficient and is unresponsive to cholinergic stimulation in tracheal tissue from preterm newborns.

Advances in perinatal care have resulted in a decline in mortality of very-low-birth-weight infants (<1.5 kilograms) and also in an extension of the mortality period. To determine the current relevance of neonatal mortality results as indicators of outcome, all deaths among 427 very-low-birth-weight infants admitted during 1975–1977 were documented. A total of 145 infants died; 90 of the deaths (62%) occurred during the early neonatal period (0 to 6 days), 35 (24%) in the late neonatal period (7 to 27 days), and 20 (14%) in the postneonatal period. Death in 17 of the 20 postneonatal losses was due to neonatal complications of prematurity, and 16 of the 20 deaths occurred during the initial hospitalization. The postponement of these deaths to the postneonatal period has important epidemiologic implications and indicates a need for a reconsideration of accepted reporting mechanisms for infants of very low birth weight.

Twelve per cent of all infants with respiratory distress admitted to our neonatal intensive-care unit from November 1973 to April 1974, were born after elective intervention (15 cesarean sections and four vaginal inductions). All were white and 18/19 were private compared to yearly admissions of white (56 per cent) and private (57 per cent). Eighteen of 19 were admitted from the region via the transport service. Mean birth weight was 2.69 kilograms, with 18 infants over 2 kilograms. Pediatric gestational age from a physical and neurological evaluation ranged from 32 to 39 weeks (mean 36.2 weeks) in contrast to obstetric dating which ranged from 38 to 44 weeks (mean 39 weeks). The obstetric dating was 3 or more weeks greater than the pediatric age in 11 infants. Pulmonary disease included transient tachypnea (5) and respiratory distress syndrome (14). No prior documentation of pulmonary maturity had been obtained in any of these infants. Mean hospitalization was 23 days (range 1 to 140), with estimated costs of $3,421 per baby. Two infants died. Respiratory distress following elective delivery remains a potent source of on-going perinatal morbidity. Regional programs must direct increased educational efforts to eliminate this preventable disease.

Explants of tracheal epithelium from each of six human neonates were exposed to both 80 and 20 oxygen under otherwise identical culture conditions. Cessation of ciliary movement and carbon particle transport occurred after 48–96 hr of exposure to 80 oxygen, but not after 168 hr of exposure to 20 oxygen.