A national two year follow up study of extremely low birthweight infants born in 1996-1997.

OBJECTIVE: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome. STUDY DESIGN: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996-1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models. RESULTS: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores. CONCLUSION: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22-26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.

Postnatal adaptation after Caesarean section or vaginal delivery, studied with the static-charge-sensitive bed.

AIM: To compare postnatal adaptation between Caesarean and vaginal deliveries, by studying sleep states, oxygenation, heart rate and body movements. Another aim was to follow the adaptation of healthy, term, vaginally born babies. METHODS: Ten vaginally born and 12 neonates born by elective Caesarean section were recorded with a movement sensor (SCSB, static-charge-sensitive bed), electrocardiogram and oximeter. The recordings started 1.5 h after birth and lasted for 12 h. For the vaginal group, another 12 h recording was performed during the third night postpartum. RESULTS: Delivery mode did not affect sleep state distribution. The vaginal group had more oxyhaemoglobin desaturation episodes <95% than the Caesarean section group (mean +/- SD: 59 +/- 10% vs 42 +/- 22% of epochs, p = 0.03), especially in active sleep, but baseline saturation was similar (96 +/- 1% vs 95 +/- 3%, p = 0.93). The vaginal group had fewer movements during sleep than the Caesarean section group (movements of 5-10 s: 5 +/- 1 h(-1) vs 10 +/- 3 h(-1), p = 0.0001). During the first 3 d, the amount of sleeping and active sleep increased, whereas wakefulness and quiet sleep decreased. Baseline oxyhaemoglobin saturation and the number of movements of over 5 s increased. CONCLUSION: Delivery mode did not affect sleep state distribution but, unexpectedly, the vaginal group had more oxyhaemoglobin desaturation events and fewer body movements than the Caesarean section group. These differences during the first postnatal day remain unexplained, but they may reflect stress and pain during labour. After a few days, changes in sleep organization, and increases in oxyhaemoglobin saturation and frequency of body movements were noted in the vaginal group, which may represent recovery and adaptation to extrauterine life.

Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants.

We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.

Speech sounds learned by sleeping newborns.

It is not yet clear whether humans are able to learn while they are sleeping. Here we show that full-term human newborns can be taught to discriminate between similar vowel sounds when they are fast asleep. It is possible that such sleep training soon after birth could find application in clinical or educational situations.

Surgical closure of patent ductus arteriosus in very-low-birth-weight infants.

In many very-low-birth-weight (VLBW) infants the ductus arteriosus fails to close spontaneously, and they subsequently develop signs and symptoms of poor tissue perfusion and heart failure. This study evalutes the results of early surgical closure of patent ductus arteriosus (PDA). We retrospectively reviewed the records of all 101 VLBW infants who weighed 1,500 g or less when their PDA was surgically ligated in Turku University Hospital between 1988 and 1998. The mean gestational age at birth was 27.2 weeks and mean birth weight 963+/-239 g. The operation was performed at 12+/-8 days of age; the infants' weight at operation was 969+/-231 g and they were tracheally extubated 11+/-14 days after the operation. The surgery-related mortality was 3% (3/101) and overall mortality 10% (10/101). We conclude that surgical closure of PDA is safe and effective in VLBW infants.

Maternal magnesium sulfate treatment is associated with reduced brain-blood flow perfusion in preterm infants.

OBJECTIVE: To examine the influence of antenatally administered magnesium sulfate (MgSO4) and ritodrine on cerebral blood flow and systemic hemodynamics in preterm infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care unit of a university central hospital. PATIENTS: Fifty-five preterm infants age <33 wks of gestation. INTERVENTIONS: Serial Doppler examinations of the brain circulation, heart rate, systemic blood pressure, and echocardiographic assessment of ductus arteriosus shunting were performed during the first week of life in infants exposed antenatally to maternal MgSO4 (n = 19) or ritodrine treatment (n = 17), and in 19 nonexposed preterm controls. MEASUREMENTS AND MAIN RESULTS: Cerebral blood flow velocity measurements were obtained from the anterior cerebral artery and internal carotid artery. Perfusion pressure and indices of resistance and blood flow in both vessels were subsequently derived. Maternal MgSO4 had no effect on neonatal cerebral blood flow velocity or resistance, but was associated with decreased (p <.05) perfusion pressure and blood flow in the anterior cerebral artery and internal carotid artery during the first day of life. Systolic blood pressure and pulse pressure were also lower (p <.05) during the whole study period in the MgSO4-exposed infants when compared with the controls. Maternal ritodrine treatment, on the other hand, had no consistent effects on either neonatal cerebral or systemic hemodynamics. CONCLUSIONS: Our data indicate that maternal MgSO4 treatment, in contrast to antenatal ritodrine, is associated with lowered cerebral perfusion in preterm infants on the first day of life.

The balance of the autonomic nervous system is normal in colicky infants.

UNLABELLED: Excessively crying, hard-to-soothe infants are described as colicky. The self-limiting course of infantile colic during early infancy suggests an etiology of transient developmental dysmaturation. It has been proposed that emotional characteristics such as temperament and self-soothing ability are correlated with the balance of the autonomic nervous system. Heart rate variability (HRV) analysis was used for evaluating the balance of the autonomic nervous system in colicky and control infants during and after the colicky period. HRV analysis was carried out on 12 colicky infants and 14 control infants at the age of 2 mo, and repeated on 10 colicky and 11 normal infants at the age of 7 mo. Measurements were performed during polygraphically confirmed slow-wave sleep (sleep stages 3 and 4). Three HRV frequency bands were defined, including a high (0.2-1.0 Hz), middle (0.12-0.2 Hz) and low (0.025-0.12 Hz) frequency variability. There were no differences between the study groups in any of the three HRV frequency bands analyzed. The high frequency variability increased significantly with age in both study groups (p = 0.009). CONCLUSION: The findings suggest that imbalance between the parasympathetic and the sympathetic nervous system is not associated with infantile colic and that, in accordance with previous findings, control of HRV shifts in a parasympathetic direction with increasing age during the first year of life.

Antenatal magnesium sulphate exposure is associated with prolonged parathyroid hormone suppression in preterm neonates.

UNLABELLED: The effects of maternal magnesium sulphate treatment on neonatal mineral status and parathyroid hormone secretory response were studied in 8 exposed and 27 control preterm infants during the first 2 wk of life. Antenatal magnesium sulphate resulted in hypermagnesaemia during the first 3-7 d of life without affecting other serum mineral concentrations. CONCLUSION: Early hypermagnesaemia was associated with hypercalciuria during the first 3 d and parathyroid hormone suppression up to the age of 2 wk in the exposed infants.

Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.

BACKGROUND: Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy). METHODS: In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint. FINDINGS: Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6). INTERPRETATIONS: Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.

Extent of fussing and colic type crying preceding atopic disease.

In a prospective follow up of 116 high risk infants, a 24 hour behavioural chart on seven consecutive days was analysed at seven and 12 weeks of age. Of children who manifested atopic disease at 2 years, 44/116 (38%), had shown significantly more fussing during the seventh, and colic type cry during the twelfth week than those who remained healthy (72/116, 62%).

Infants with colic have a normal sleep structure at 2 and 7 months of age.

OBJECTIVE: To compare nighttime sleep structure between infants with colic and a control group. STUDY DESIGN: Sleep and cry times of 15 infants with colic and 16 infants in a control group were recorded with the use of a daily diary at the ages of 5 weeks and 6 months. The diary was kept at home for a 1-week period. Overnight polygraphic sleep recordings in a sleep laboratory were performed when the infants were 2 months of age and were repeated for 11 infants with colic and 14 infants in a control group at 7 months of age. RESULTS: Daily sleep time was shorter in infants with colic compared with the control group at 5 weeks of age (P =.001). Polygraphic data showed a similar sleep structure between the study groups at 2 and 7 months of age. Infants with colic had somewhat more obstructive apneas during rapid eye movement sleep at the age of 2 months (P =.04), and they had fewer awakenings at the age of 7 months than the control group (P =.003). CONCLUSION: Infants with colic had normal sleep polygraphic finding at 2 and 7 months of age including sleep structure, movements, and breathing. Despite the shorter reported daily sleep times, the polygraphic data did not suggest infantile colic to be associated with a sleep disorder.

Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.

BACKGROUND: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. OBJECTIVE: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. METHODS: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. RESULTS: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03). The differences were not detected by bacterial cultivation. CONCLUSION: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.

A national short-term follow-Up study of extremely low birth weight infants born in Finland in 1996-1997.

OBJECTIVES: The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996-1997, and to analyze risk factors associated with poor outcome. PARTICIPANTS AND METHODS: The study population included all stillborn and live-born ELBW infants (birth weight: <1000 g; gestational age: at least 22 gestational weeks [GWs]), born in Finland between January 1, 1996 and December 31, 1997. Surviving infants were followed until discharge or to the age corresponding with 40 GWs. National ELBW infant register data with 101 prenatal and postnatal variables were used to calculate the mortality and morbidity rates. A total of 32 variables were included in risk factor analysis. The risk factors for death and intraventricular hemorrhage (IVH) of the live-born infants as well as for retinopathy of prematurity (ROP) and oxygen dependency of the surviving infants were analyzed using logistic regression models. RESULTS: A total of 529 ELBW infants (.4% of all newborn infants) were born during the 2-year study. The perinatal mortality of ELBW infants was 55% and accounted for 39% of all perinatal deaths. Of all ELBW infants, 34% were stillborn, 21% died on days 0 through 6, and 3% on days 7 though 28. Neonatal mortality was 38% and postneonatal mortality was 2%. Of the infants who were alive at the age of 4 days, 88% survived. In infants surviving >12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight <600 g and gestational age <25 GWs were the independent risks for death and short-term disability. The primary risk factor for IVH grades II through IV was RDS. Low 5-minute Apgar scores predicted poor prognosis, ie, death or IVH, and antenatal steroid treatment to mothers with threatening premature labor seemed to protect infants against these. Some differences were found in the mortality rates between the 5 university hospital districts: neonatal mortality was significantly lower (25% vs 44%) in one university hospital area and notably higher (53% vs 34%) in another area. Furthermore, significant differences were also found in morbidity, ie, oxygen dependency and ROP rates. Differences in perinatal (79% vs 45%) and neonatal (59% vs 32%) mortality rates were found between secondary and tertiary level hospitals. CONCLUSION: Our study shows that even with modern perinatal technology and care, intrauterine and early deaths of ELBW infants are common. The outcome of infants born at 22 to 23 GWs was unfavorable, but the prognosis improved rapidly with increasing maturity. The clear regional and hospital level differences detected in survival rates and in short-term outcome of ELBW infants emphasizes that the mortality and morbidity rates should be continuously followed and that differences should be evaluated in perinatal audit procedures. (ABSTRACT TRUNCATED)

Antenatal and early postnatal dexamethasone treatment decreases cortisol secretion in preterm infants.

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.

Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months.

AIM: To evaluate the role of intestinal microflora and early formula feeding in the maturation of humoral immunity in healthy newborn infants. STUDY DESIGN: Sixty four healthy infants were studied. Faecal colonisation with Bacteroides fragilis group, Bifidobacterium-like, and Lactobacillus-like bacteria was examined at 1, 2, and 6 months of age, and also the number of IgA-secreting, IgM-secreting, and IgG-secreting cells (detected by ELISPOT) at 0, 2, and 6 months of age. RESULTS: Intestinal colonisation with bacteria from the B fragilis group was more closely associated with maturation of IgA-secreting and IgM-secreting cells than colonisation with the other bacterial genera studied or diet. Infants colonised with B fragilis at 1 month of age had more IgA-secreting and IgM-secreting cells/10(6) mononuclear cells at 2 months of age (geometric mean (95% confidence interval) 1393 (962 to 2018) and 754 (427 to 1332) respectively) than infants not colonised (1015 (826 to 1247) and 394 (304 to 511) respectively); p = 0.04 and p = 0.009 respectively. CONCLUSIONS: The type of bacteria colonising the intestine of newborns and the timing may determine the immunomodulation of the naive immune system.

Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants.

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (<2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.

Neonatal monitoring after maternal fentanyl analgesia in labor.

OBJECTIVE: To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor. METHODS: 12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed. RESULTS: The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004). CONCLUSIONS: Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.

Transforming growth factor-beta in breast milk: a potential regulator of atopic disease at an early age.

BACKGROUND: According to data from animal and in vitro studies, transforming growth factor-beta (TGF-beta) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. OBJECTIVE: We sought to ascertain whether TGF-beta in breast milk is associated with specific IgA production and atopic disease in human subjects. METHODS: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-beta1 and TGF-beta2 in maternal colostrum, mature milk, and the infants' sera were determined. The enzyme-linked immunospot assay was used to assess the infants' specific IgA production in response to beta-lactoglobulin, casein, gliadin, and ovalbumin. RESULTS: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-beta1 and TGF-beta2 were higher in maternal colostrum, but not in mature milk and infants' serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease (P =.0008 and P =. 015, respectively). The concentration of TGF-beta2 was, and that of TGF-beta1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells (P =.048 and P =.076, respectively). CONCLUSION: TGF-beta in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects.

Influence of maternal magnesium sulphate and ritodrine treatment on the neonate: a study with six-month follow-up.

Magnesium sulphate and ritodrine are commonly used drugs in the prevention of preterm delivery. However, the effects of these treatments on the newborn are controversial. It has previously been suggested that antenatal tocolytic magnesium sulphate decreases the incidence of cerebral palsy, but increases paediatric mortality. On the other hand, antenatal ritodrine treatment has been reported to increase the incidence of neonatal peri-intra-ventricular haemorrhage (PIVH). We investigated the cerebral ultrasonographic findings, neurological outcome and apparent life-threatening events (ALTE) among 63 infants, born before 33 wk of gestation, whose mothers were antenatally treated for premature birth with ritodrine or magnesium sulphate, and for pre-eclampsia with magnesium sulphate. Cerebral ultrasonography was performed during the first week of life and repeated before hospital discharge. The pathological findings were confirmed by a paediatric radiologist. A paediatrician and a physiotherapist performed the neurological follow-up examination of the survivors at 6 mo of age. We found Grade 3-4 PIVH in 15% of the infants exposed to maternal ritodrine treatment, in 9% of the infants whose mothers received tocolytic magnesium treatment, and in none of those exposed to maternal magnesium treatment for pre-eclampsia (p = 0.19). However, no differences were observed in 6-mo development or in the rate of paediatric mortality and ALTE among these three study groups. Because of the retrospective design and the limited number of subjects, the results of this study must be interpreted with caution.