Tocolytic effectiveness of nifedipine versus ritodrine and follow-up of newborns: a randomised controlled trial.

BACKGROUND: Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found no difference in psychosocial and motor functioning. In a randomised, multicentre trial, we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long-term follow-up of the newborns after 2 years of age. METHODS: Patients with imminent preterm labour were randomised and received either nifedipine or ritodrine. Side-effects, tocolytic effectiveness and neonatal outcome were studied. Development of the children was studied after the age of 2 years by a parental questionnaire. RESULTS: Ninety-three patients were included. Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group (p=0.4). Patients who received ritodrine experienced significantly more side-effects compared to patients who received nifedipine (29 versus 4%, p<0.05). No significant differences were found in either group for average birth weight, Apgar scores after 1 min, neonatal intensive care unit (NICU) admission and neonatal complications. Parental questionnaires after 2 years had a response rate of 70%. Two-thirds of the children had developed normally in both groups. In both groups, only a few children were severely retarded (n=4). No significant differences in development were found between the 2 groups. CONCLUSIONS: Both nifedipine and ritodrine proved effective tocolytic drugs, however ritodrine caused significantly more maternal side-effects. Neonatal outcome and long-term development after 2 years of age were not significantly different. We favour nifedipine over ritodrine as a tocolytic drug.

Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years.

BACKGROUND: Children born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW, <1500 g; hereafter called VP/VLBW) are at risk for behavioural and emotional problems during school age and adolescence. At school entrance these problems may hamper academic functioning, but evidence on their occurrence at this age in VP/VLBW children is lacking. AIM: To provide information on academic functioning of VP/VLBW children and to examine the association of behavioural and emotional problems with other developmental problems assessed by paediatricians. DESIGN, SETTING AND PARTICIPANTS: A cohort of 431 VP/VLBW children aged 5 years (response rate 76.1%) was compared with two large national samples of children of the same age (n = 6007, response rate 86.9%). OUTCOME MEASURES: Behavioural and emotional problems measured by the Child Behavior Checklist (CBCL), and paediatrician assessment of other developmental domains among VP/VLBW children. RESULTS: The prevalence rate of a CBCL total problems score in the clinical range was higher among VP/VLBW children than among children of the same age from the general population (13.2% v 8.7%, odds ratio 1.60 (95% confidence interval 1.18 to 2.17)). Mean differences were largest for social and attention problems. Moreover, they were larger in children with paediatrician-diagnosed developmental problems at 5 years, and somewhat larger in children with severe perinatal problems. CONCLUSION: At school entrance, VP/VLBW children are more likely to have behavioural and emotional problems that are detrimental for academic functioning. Targeted and timely help is needed to support them and their parents in overcoming these problems and in enabling them to be socially successful.

Hypotriploidy 68,XX: a new case report and review of earlier cases.

We report a prematurely born patient with a 68,XX karyotype. She presented with syndactyly of 2nd and 3rd toes, minor facial features, microcephaly, slender hands, bicuspid aortic valve, patent ductus arteriosus and hypotonia. Comparison with other reported cases is given.

Validation of a Dutch language screening instrument for 5-year-old preterm infants.

AIM: The validation of the Dutch Taal Screenings Test (TST), a language-screening test, which is included in a follow-up instrument developed to enable paediatricians to assess 5-y-old preterm infants for their motor, cognitive and speech and language development. METHODS: The speech and language development of 145 5-y-old infants born before 32 wk of gestation and/or with a birth weight of less than 1500 g was assessed by a paediatrician using the TST and by a speech therapist using standardized language tests. RESULTS: All correlations between the instruments were significant. Using the original cut-off point of the TST for abnormal speech and language development (18 points), the paediatrician will only identify 62% of the children who need speech therapy. For this group of children, a cut-off point of 17 is more effective. The positive predictive value of the TST improved from 77% to 82% by using a parent and school questionnaire to evaluate in a more subjective way the speech and language development. CONCLUSION: Using the TST, paediatricians will be able to identify speech or language problems in 5-y-old preterm infants.

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Intraventricular haemorrhage in utero. A case-report and review of the literature.

Intraventricular haemorrhages (IVH) are the most commonly occurring intracranial haemorrhages in neonates, especially in preterm infants. The origin of IVHs is located in the germinal matrix. The cause of an IVH is a combination of intravascular, vascular and extravascular factors. The diagnosis is made by ultrasound. Knowledge on the causes of antenatal haemorrhages lags far behind knowledge on the causes of postnatal haemorrhages. In cases of haemodynamic changes in utero, ultrasound could be useful to examine the foetal brain. The presence of an intracranial haemorrhage in utero greatly influences the prognosis of the infant.

Nifedipine versus ritodrine for suppression of preterm labor; a meta-analysis.

BACKGROUND: Since large randomized clinical trials comparing the effectiveness of nifedipine and ritodrine in the suppression of preterm labor are lacking, we performed a meta-analysis on the subject. METHODS: We searched the databases Medline and EMBASE using the keywords 'nifedipine', 'ritodrine' and 'randomized' or 'randomised'. The studies were scored for blinding, method of randomization and type of analysis ('intention-to-treat' versus 'par protocol'). Subsequently, two by two tables were constructed using 'delay of labor by 48 hours or more', 'delay of labor beyond 36 weeks gestation', perinatal mortality, respiratory distress syndrome and admission to a neonatal intensive care unit as end points. Homogeneity between the studies was tested with a Breslow-Day test. Pooled odds ratios were calculated in case homogeneity could not be rejected. RESULTS: We could detect ten studies that were published between 1986 and 1998, incorporating data of 681 patients. Nifedipine reduced the risk of delivery within 48 hours compared to ritodrine, but this difference was not statistically significant (odds ratio 0.85, 95% confidence interval 0.54 to 1.1). Nifedipine also reduced the risk of delivery before 36 weeks compared to ritodrine, and this difference was statistically significant (odds ratio 0.59, 95% confidence interval 0.39 to 0.90). We are not aware of studies reporting on long-term outcome. CONCLUSION: Since studies reporting on long-term outcome are lacking, the choice between nifedipine and ritodrine can only be based on obstetrical and short-term neonatal outcomes. From that perspective, nifedipine should be the drug of first choice for the suppression of preterm labor.

A randomized comparison of nifedipine and ritodrine for suppression of preterm labor.

OBJECTIVES: To compare the efficacy and safety of nifedipine and ritodrine in preventing preterm labor, and to evaluate maternal side effects and neonatal outcome. STUDY DESIGN: Non-blind, randomized controlled trial RESULTS: A randomized trial of 102 pregnant women with gestational ages under 34 weeks, including 24 with twin pregnancies and 45 on betasympathicomimetic drugs, who had regular uterine contractions with either observed cervical changes or preterm rupture of membranes. After stratification women were randomly assigned to receive either ritodrine intravenously or nifedipine orally. Fifty-five women were randomized to the nifedipine group and 47 to the ritodrine group. As expected, both groups were comparable in terms of several entry variables, including mean gestational age, ruptured membranes, treatment with tocolytic drugs, cervical examination, contraction frequency, age, and twin gestation. Delivery of women in the nifedipine group was delayed for 48 h, 7 days, and until 34 weeks gestation in 33 (60%), 26 (47%) and 21(38%) cases, respectively, compared with 31 (66%), 21(45%) and 11(23%) women in the ritodrine group (no significant difference). Maternal side effects were significantly less common in the nifedipine group than in the ritodrine group, however after 7 days of therapy there was no difference between the two groups. Neonatal outcome was similar in the two groups, with four neonatal deaths in the nifedipine and five in the ritodrine group. CONCLUSIONS: Nifedipine seems to be as effective as ritodrine in the treatment of preterm labor and is associated with less frequent side effects.

Foregoing intensive care treatment in newborn infants with extremely poor prognoses. A study in four neonatal intensive care units in The Netherlands.

Within the framework of the broader ethical discussion on end-of-life decision making in neonatology and the need to obtain more quantifiable data, we performed a multicenter study in four Dutch neonatal intensive care units. All infants who died in these units in 1993 were included in the study. Aside from cases in which foregoing treatment was not under discussion, cases in which death appeared inevitable (A cases) and cases in which foregoing treatment because of extremely poor prognosis was the decisive factor (B cases) were distinguished. A total of 181 neonatal deaths occurred. Thirty-five infants died even after full continuation of treatment. In 98 A cases and 48 B cases, which together represented 81% of all deaths, treatment was foregone either because the infants had no chance to survive or because of extremely poor prognoses. In these cases, the medical team ultimately achieved consensus of opinion, although in some instances several sessions were required. In three cases, the parents did not agree with the team advice. In one A case death appeared inevitable. In two B cases, the parents' wish to continue treatment was followed. In a large majority of B cases, the decisions to forego treatment were based on the presence of severe cerebral damage. In A cases there was no real choice because death appeared inevitable. However, in B cases neonatologists were obliged to determine whether continuation of treatment was justifiable or if withdrawal of treatment in view of extremely poor prognoses was preferred.

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

[Continuation or withdrawal of life-sustaining procedures in newborn infants: a study in 4 centers for neonatal intensive care]. / Voortzetten of staken van levensverlengend handelen bij pasgeborenen: een onderzoek in 4 centra voor neonatale intensieve zorg.

OBJECTIVE: To provide data about continuation or withdrawal of life sustaining therapy in the critical ill newborn. METHOD: Retrospective examination of the histories of all 185 patients who died during the year 1990 (17% of total admissions) in 4 out of the 10 neonatal intensive care units in the Netherlands. RESULTS: The mean gestational age was 31.9 weeks (range 23-43; SD 5.5) and the mean birth weight 1827 g (455-5820; SD 1105). 136 infants were prematurely born, 49 full term. Intensive care was not started in 17 (9%) of the 185 patients and intensive care was withdrawn in 58 patients (31%) because there was no chance of survival. Therapy was withdrawn because of the poor prognosis for the quality of later life in 35 patients (19%). Intensive therapy was continued until death occurred in 74 infants (40%). Respiratory and circulatory problems, infections and severe acquired neurological damage were the main causes of death (32%, 17%, 19% and 24% of the cases respectively). In the cases of death due to respiratory and circulatory failure treatment was continued as long as possible. In infants who died with neurological damage as the main diagnosis, treatment was withdrawn because of the poor prognosis for the quality of life in 25 out of 44 infants. CONCLUSION: Life sustaining therapy was withdrawn or not started in 5% of the patients admitted because there was no chance of survival and in 3% because of a poor prognosis for the quality of later life.

[Prevention and treatment of respiratory distress syndrome in premature infants using intratracheally administered surfactants]. / Preventie en behandeling van het 'respiratory distress syndrome' bij vroeggeborenen door intratracheale toediening van surfactans.

OBJECTIVE: To study the effects of administration of surfactant immediately after birth (prophylactic) or after 6 hr (therapeutic) to 81 Dutch preterm infants from a multicentre trial. SETTING: University Hospital Leiden and Sint Joseph Hospital, Veldhoven. DESIGN: A randomized controlled trial with stratification for biochemical lung (im)maturity. The aims of the study were (I): to improve the TcPO2/FiO2 ratio by 40% and (2) to prevent the respiratory distress syndrome by 50% at 6 hours after birth. The secondary goal was to compare effects of prophylactic versus therapeutic use of exogenous surfactant (from 6 hours onwards) in surfactant-deficient infants. PATIENTS: The entrance criteria of the study were: (I) inborn children with a gestational age between 26 and 30 weeks, (2) elective intubation and (3) sampling of bronchotracheal or gastric aspirate. After randomization the children received surfactant within 10 minutes after birth prophylactically (n = 42) or 6 hours after birth if they needed more than 60% oxygen (13 of 39 control infants). A second dose of surfactant was given if, at 6 hours after the first dose, the FiO2 was still high (> or = 0.6). TREATMENT: We used a natural porcine surfactant preparation (Curosurf) in a dose of 200 mg/kg given through the endotracheal tube. RESULTS: The mean gestational age of the 81 infants was 28.2 weeks. The TcPO2/FiO2 ratios increased in the prophylactic group compared with the controls (38 versus 30 kPa; p < 0.05). RDS occurred less often and less severely in the prophylactic group (p < 0.05). Neonatal mortality was lower in the prophylactically treated infants (3/42) than in the control group (10/39; p < 0.05). Compared with the control infants with immature lungs, the immature prophylactically treated infants had six hours after birth higher TcPO2/FiO2 ratios (35 vs 13 kPa; p < 0.001), a 35% reduction of the incidence of RDS with a significant reduction of its severity (p < 0.05), and significantly lower mean airway pressures (0.87 versus 1.24 kPa; p < 0.005). The surfactant given 6 hours after birth to the immature controls resulted in an immediate improvement of the oxygenation. Nevertheless, these infants spent more time on the respirator and needed extra oxygen for longer periods than the immature infants prophylactically treated (p < 0.05). CONCLUSION: Surfactant, given either prophylactically or therapeutically, results in clinical improvement of children with biochemically immature lungs. A prophylactic treatment, moreover, results in reduced incidence and severity of RDS, in a significant shortening of the time spent on the respirator and in reduced need of extra oxygen compared with therapeutic treatment. We recommend to give surfactant prophylactically or at the first signs of RDS.

[Transcutaneous PCO2 determination in neonatology]. / Transcutane PCO2-meting in de neonatologie.

Transcutaneous PCO2 studies were performed in 21 healthy preterm infants and in 12 preterm infants with respiratory problems, in order: I. to evaluate the feasibility of transcutaneous PCO2 measurements in the clinical situation; 2. to collect normal values for preterm infants, and 3. to compare transcutaneous tcPCO2 values with PCO2 measured in capillary or arterial blood samples. Normal tcPCO2, measured in 21 healthy preterm infants, mean gestational age 32.5 +/- 2.3 weeks (range 26 6/7-36 1/7, mean birth weight 1547 +/- 498 gram (range 820-2840), postnatal age 2.2 +/- 2.1 days (range 0-6) was 41.2 +/- 5.5 mm Hg. The relation between transcutaneous PCO2 and PCO2 in arterial or capillary blood samples was studied in 12 patients with respiratory problems, 7 boys and 5 girls, mean gestational age 31 4/7, birth weight 1600 gram (range 885-3050). We found a good linear relation between tcPCO2 and arterial PaCO2 (regression coëfficient between 0.66 and 0.96) and a bad correlation between tcPCO2 and capillary PCO2 (regression coefficient 0.14-0.89). We conclude that tcPCO2 measurement is reliable and feasible for clinical use and is more reliable than PCO2 measurement in capillary blood.

Lung function 8-18 years after intermittent positive pressure ventilation for hyaline membrane disease.

Lung function and respiratory symptoms were studied in 40 children aged 8-18 years who had been ventilated for hyaline membrane disease after birth; 11 had had bronchopulmonary dysplasia. Also studied were 38 age matched children who had had hyaline membrane disease but had not required ventilation, 25 unmatched children who were born prematurely but did not develop hyaline membrane disease, and 39 randomly selected pupils of similar age. There was no difference in thoracic gas volume, total lung capacity, inspiratory vital capacity, residual volume, or transfer factor for carbon monoxide between the groups. Respiratory symptoms during the three years before the study and the frequency of clinically diagnosed asthma in patients and their family were similar in all the children with hyaline membrane disease irrespective of whether they had been ventilated or had had bronchopulmonary dysplasia. The children with bronchopulmonary dysplasia, however, had a lower forced expiratory volume in one second (FEV1) before bronchodilator (73% predicted) than the other groups (88-95% predicted). Children who had required ventilation had lower values for specific airways conductance (sGaw) and a greater increase in FEV1 (delta FEV1) after salbutamol (13%) than non-ventilated children (6%); delta FEV1 was associated with the peak pressure of intermittent positive pressure ventilation, a family history of asthma and a history of wheezing, recurrent respiratory illnesses, and a doctor's diagnosis of asthma during the three years before the study. These findings indicate that after eight years of age patients with bronchopulmonary dysplasia have more reversible airways obstruction, compatible with increased bronchial smooth muscle tone.

Circadian rhythms in preterm infants: a preliminary study.

A method has been developed for long-term continuous recordings of several physiological variables in humans, including body movements, core temperature, heart rate and respiratory rate. This method enabled us to study circadian rhythms of body temperature and rest-activity in preterm infants. In 5 out of 9 infants (recorded at 28-34 weeks conceptional age) circadian rhythms were found in body temperature. We conclude that circadian rhythmicity is present during the early neonatal period in certain physiological variables (body temperature) but not in others (rest-activity).