Kirsti Heinonen

Clinically symptomatic central venous catheter-related deep venous thrombosis in newborns

Salonvaara M, Riikonen P, Kekomäki R, Heinonen K. Clinically symptomatic central venous catheter‐related deep venous thrombosis in newborns. Acta Pædiatr 1999; 88: 642‐6. Stockholm. ISSN 0803‐5253

Determinants of bone mineral density in prematurely born children aged 6-7 years.

The aim of this study was to assess the long‐term effects of prematurity and growth during the first year on bone mineralization in prematurely born children. The study group consisted of 38 prematurely born Finnish children (17M, 21F) examined at the age of 6‐7 y. After birth, all children were fed with banked human milk until discharge from hospital. Thereafter, 27 children were partially breastfed until the age of 5–7 months. Infants with gestational age (GA) <33 weeks (n = 25) received calcium 45‐50 mg/100 kcal, phosphorus 40‐45 mg/100 kcal, vitamin A 1000 IU/d, vitamin C 2 mg/d and vitamin D 400 IU/d until 2.5 kg. Infants born > 33 weeks received only vitamin D 400 IU/d. Bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X‐ray absorptiometry (DXA) of the lumbar spine (L2‐L4) at 6‐7 y of age. At examination, all children had normal height and weight. BMD values were within the confidence interval of the Finnish reference values. In regression analysis bone area, present weight, GA and weight at 1 y were the most significant factors explaining 77.1% of the variance of BMC. After adjusting for other independent variables the prematurely born children who were thinner at 1 y of age subsequently had higher BMC values when examined at the age of 6‐7 y. This study shows that growth patterns during the first year of life have long‐term effects on bone mineralization.

Intrauterine growth retardation (IUGR) in pre-term infants

A representative sample (N = 120, 96%) of all pre-term (gestational age less than or equal to 36 weeks) infants born alive to mothers resident in the province of Kuopio, Finland, during a two year period, were studied at birth to evaluate the signs of intrauterine growth retardation (IUGR). Norms for somatic growth were based on measurements of birth weight, length and Ponderal Index (100 X birth weight (g) X birth length (cm)-3) of 51 pre-term singletons, born to healthy mothers after uncomplicated pregnancies, in relation to whom there were no discrepancies between menstrual dates and pediatric assessment of gestational age. The lower limits for normal ranges were defined as values two standard deviations below the expected means for the gestational age. Pre-term IUGR was diagnosed if birth weight and/or birth length and/or PI were more than 2 SD below the expected mean for gestational age. Different types of IUGR were found in 49 pre-term infants (41% of the pre-term population). A low PI was the most common descriptor of IUGR, being present in 42 out of 49 infants. A third of infants had more than one indicator of IUGR. In this population, pre-term IUGR was strongly associated with perinatal maternal pathology (especially hypertension, toxemia and prolonged leakage of amniotic fluid). The neonatal morbidity and mortality among pre-term IUGR infants was markedly higher than that among appropriately grown pre-term infants with corresponding gestational age. There were significantly more cases with fatal intraventricular hemorrhage in pre-term IUGR than in pre-term normally-grown infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence, predictive factors and associated morbidity of broncho-pulmonary dysplasia in a preterm birth cohort

The occurrence, predictive factors and associated morbidity of bronchopulmonary dysplasia (BPD) was examined in a preterm birth cohort of 712 children, born before 37 weeks of gestation to residents of a geographically defined area between 1978-82. All cases of BPD (N = 16) were born at or before 32 weeks of gestation. The incidence of BPD, based on status at the age of 28 days, was 1 per 1000 live births, but 135 per 1000 live preterms born at or before 32 weeks. Most cases of BPD developed following respiratory distress syndrome (RDS), only one case developing after minimal respiratory symptoms was observed. BPD infants had higher neonatal morbidity, even when compared with preterms of equal gestational maturity, but only a few variables had predictive value with respect to the future development of BPD. Radiologic grading of RDS and associated early cardiologic signs did not increase their predictivity regarding the subsequent development of BPD. Two (12.5%) of the 16 BPD infants died postneonatally. The unfavorable effects of BPD on the health status of preterm infants extended far beyond the neonatal period. The BPD group, which consisted only of 18% of neonatal survivors born at less than or equal to 32 weeks, consumed 53% of all hospital days used by these preterms during the first two years of life. In particular, BPD survivors had markedly more respiratory infections (63%), more neurologic sequelae (37%) and more cases of retrolental fibroplasia (12%) than their non-BPD counterparts.

Neurodevelopmental screening of in utero growth-retarded prematurely born children before school age.

As part of a prospective follow-up study of two premature cohorts (gestational age ≤36 weeks) born between 1976 and 1977, designed to evaluate the effects of IUGR on morbidity, mortality and neurological development in prematurely born children, 71 prematurely born children (48 AGA, 23 IUGR) without major neurological handicaps were subjected to detailed assessment of their neurological and psychological status at the age of 4 years. Thirty-six healthy full-term children formed a control group. The socioeconomic status of the families of the premature groups was similar to that of the families of the control group. The assessment consisted of a neurodevelopmental screening test and four psychological tests. Validation of the NDS test in relation to proven cognitive problems (sensitivity 96%, specificity 64%, relative risk 16.74) and determination of normal ranges were based on findings in the control group. There were significantly more children with moderate to high risk scores (≥10) among the IUGR group than among the AGA group. The neurodevelopmental profile of the preterm IUGR group was characterized by complex deviations of motor, visual and perceptual functions from normal. Preterm AGA children had only slightly higher risk scores in relation to fine motor, upper motor and perceptive functions than control children. Of the various perinatal factors studied, IUGR (especially in relation to boys who needed respirator therapy) was the most likely to be associated with abnormal NDS scores before school age.

Prematurity-associated morbidity during the first two years of life: a population-based study

ABSTRACT. Two‐year patterns of postneonatal morbidity, both chronic and non‐chronic, are reported for all liveborn preterm infants (n=612; malformations excluded) delivered in the province of Kuopio, Finland, between 1978 and 1982. The overall readmission rate was 30%, the commonest causes being respiratory infections, surgical disorders (inguinal hernias) and neurological problems. The higher readmission rate in preterms born at ≦33 weeks of gestation was due to a larger proportion of children being admitted with chronic prematurity‐associated conditions; preterms without chronic disabilities had similar rates of readmission irrespective of gestational age. Neonatal treatment variables were of little help in the identification of children requiring readmission after neonatal care. Instead, intrauterine growth retardation (IUGR) or being of the male sex significantly increased the risk of subsequent read‐mission.

Intraventricular haemorrhage in very-low-birthweight preterm infants: association with low prothrombin activity at birth.

AIM To determine the occurrence of intraventricular haemorrhage (IVH) and its association with coagulation factors at birth in preterm neonates born before 30 wk gestation. METHODS 38 neonates (median gestational age 27 wk, range 24-29 wk; median birthweight (BW) 933 g, range 515-1760 g) admitted to the neonatal intensive care unit were studied. Blood samples for coagulation factors were taken within 2 h after birth. The first cranial ultrasonographic examination was performed within the first 3 d. The occurrence of IVH was tested statistically by the Mann-Whitney U-test for association with the activity of coagulation factors and clinical variables. RESULTS Thirteen IVHs occurred within the first 3 d of life. IVH was associated with BW <1000 g (p=0.012), low mean blood pressure within the first 2 d (p=0.026), gestational age <27 wk (p=0.054), low Apgar scores (<7) at 1 min (p=0.078) and intrauterine growth restriction (p=0.072). At birth (samples drawn with a median of first 36 min of life), infants with subsequent IVH had statistically significantly lower prothrombin (factor II) activity (p=0.024) than infants without IVH. CONCLUSION The measured low prothrombin may have been affected by a prior bleeding event. Nevertheless, preterm infants with low prothrombin activity may be susceptible to IVH, or to the progression of it, if left undiagnosed.

Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months

The development of the coagulation and anticoagulation system in preterm infants was assessed, with special emphasis on extremely low birth weight (ELBW) infants and haemorrhagic or other complications after birth. Coagulation factors II (prothrombin), V (FV), VII (FVII) and X (FX) were analysed at birth and at a corrected age of six months. In addition, antithrombin (AT), protein C (PC) and protein S (PS) were measured at six months, and DNA samples were tested for Factor V Leiden (R506Q). Eighty-two infants, with a median gestational age (GA) of 32 weeks (range 24-36) and a median birth weight of 1562 g (range 695-3520), were studied. Fifteen of these were ELBW infants (range 695-1000g). Prothrombin, FV, FVII and FX reached healthy term six-month-old infant activity levels. Prothrombin and FX did not reach adult values; median activity levels remained at 82% and 78%, respectively. During the follow up, the FV and FVII levels of the ELBW infants (GA 24-27 weeks) increased more than those of the preterm infants born with higher GA (p < 0.001). At birth, prothrombin correlated significantly with FV, FVII and FX (p < 0.001). FVII at birth and at six months correlated significantly with PC (p = 0.021 and p = 0.009, respectively). These findings indicate that the gain in the coagulation factor concentrations in infancy is greatest in infants with the lowest GA at birth. Interesting new inter-relations of coagulation factor and physiological anticoagulant levels may indicate that there are still unrecognised pathways in the function of newborn haemostasis.

Dexamethasone Pretreatment Attenuates Cerebral Vasodilative Responses to Hypercapnia and Augments Vasoconstrictive Responses to Hyperventilation in Newborn Pigs

In the perinatal period, glucocorticoids are frequently administered to enhance pulmonary maturity or prevent chronic lung disease of prematurity. Recently, it has been suggested that the perinatal exposure to glucocorticoids can be associated with unfavorable neurologic development. We studied the hypothesis that 24-h pretreatment with glucocorticoid might modify cerebrovascular responses to high and low partial arterial CO2 tension in newborn animals in vivo. A closed cranial window was implanted over the left parietal cortex of 20 anesthetized ventilated newborn (<3 d old) pigs. The actual experiments were carried out in 15 pigs: eight pretreated with a total dose of 6 mg/kg of dexamethasone and seven controls. Five pigs were used for preliminary experiments as described in the text. Pial arteriolar diameters were measured during 1) baseline conditions (normocapnia), 2) hypercapnia induced by ventilating the animals with a gas mixture containing 10% CO2, or 3) hyperventilation with resultant hypocapnia. Under these conditions, the concentrations of 6-keto-PGF1α in the CSF were measured in five experimental animals and six controls. In summary, the dexamethasone pretreatment 1) attenuated the hypercapniainduced dilator responses of pial arterioles and prevented the hypercapnia-associated fall in mean arterial blood pressure; 2) caused moderate, although not statistically significant, diminution in 6-keto-PGF1α levels in the CSF during baseline; 3) blocked hypercapnia-induced elevation of 6-keto-PGF1α; and 4) enhanced vasoconstrictive arteriolar responses to hyperventilation. We speculate that in the clinical setting, the dexamethasone effects may compromise the adjustments of global or regional cerebral blood flow to changing physiologic states in neonates.

INITIAL SYSTOLIC TIME INTERVALS AS PREDICTORS OF THE SEVERITY OF TRANSIENT TACHYPNEA IN TERM NEONATES

ABSTRACT. 42 term neonates with transient tachypnea (TTN) underwent echocardiography and determination of systolic time intervals before the age of 4 hours. Based on initial measurement of right ventricular systolic time intervals (RVSTIs) the patients were divided in two groups: neonates with RVSTI ratios <0.50 (Group I) (n=35) and neonates with RVSTI ratios >0.50 (Group II) (n=7). Group II neonates also had significantly more prolonged left ventricular systolic time intervals (LVSTIs) than Group I neonates. Group II neonates developed markedly more severe form of TTN than Group I neonates. Initially prolonged RVSTI was best predictor of the development of severe TTN (relative risk ratio 17.5, p<0.001): clinical characteristics and oxygen requirements at the admission had limited predictive value.