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BACKGROUND: Small for gestational age (SGA) extremely low birthweight (ELBW < 1000 g) survivors often remain small and/or have subnormal school performance. Some are twins/triplets with larger appropriate size for gestational age (AGA) co-twins/triplets. OBJECTIVE: To assess whether SGA ELBW twins/triplets remain different from their AGA co-twins/triplets. DESIGN, SETTING: During 1981-1999, 353 SGA ELBW neonates were admitted to our neonatal intensive care unit: 267 survived, 54/267 were twins/triplets, and 36/54 had AGA surviving co-twins/triplets. This longitudinal study describes the growth, neurodevelopmental outcome, and school performance of these 36 sets (3-17 years). The children were classified as normal, or having minor, moderate, or severe deficiencies. RESULTS: Values for birth weight (mean intrapair z score difference 2.26), length (2.74), and head circumference (2.62) were lower in SGA neonates than in AGA co-twins/triplets. SGA survivors remained smaller at 3-6 years of age: mean intrapair z score difference in weight, 1.37, height, 1.54, head circumference, 1.21. From 6 to 17 years, smaller differences persisted. Former SGA children had a tendency to have motor deficiencies (nine SGA v three AGA) and mental retardation (seven v four), same hearing loss (two v two), but significantly more visual abnormalities (15 v 11), behavioural disturbances (14 v five), and speech problems (14 v eight). Twenty four sets were in the same normal level class, often supported by familial/professional help. CONCLUSIONS: Although raised in the same environment, SGA ELBW survivors remained smaller and had more visual/behavioural/speech problems, but most maintained grade level parity with their AGA siblings, with appropriate help.

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The very early establishment of certain sensory faculties turns the fetus into a being capable of perceiving multiple stimuli. This perceptive capability forms part of many interchanges between the mother and her developing child. These interchanges are doubtless not only biological and metabolic in nature, but also sensorial and sensitive. The importance of a good quality of psychoaffective communication between mother and child during pregnancy has been shown to be decisive for fetal growth and also for the perinatal period and further development of the child. Maternal psychological stress leads to adverse pregnancy outcome. Chronic anxiety causes an increased stillbirth rate, fetal growth retardation and altered placental morphology. Experimental studies have demonstrated a relationship between specific episodes of maternal psychological stress and exacerbation of fetal asphyxia in utero. It is concluded that all the psychoaffective interchanges between the mother and child are decisive for harmonious fetal growth and brain development.

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OBJECTIVE: To compare the family status and neurodevelopment of triplets conceived by spontaneous pregnancy (SP), ovarian stimulation (OS), in vitro fertilization (IVF), and gametal intra-fallopian transfer (GIFT). DESIGN: A follow-up study consisted of neurodevelopmental examination and/or of interviews of parents/pediatricians/teachers and social workers. Outcome of the children was categorized as defective (mild, moderate, severe) or normal. SETTING: The Port-Royal neonatal unit and follow-up clinic. SUBJECTS: From 1/01/1987 to 31/12/94, one to all three neonatal triplets were admitted to the Port-Royal neonatal unit. Pregnancy was SP in 12, OS in 24, IVF in 36, GIFT in 5. All survivors (36 SP, 68 OS, 98 IVF, 14 GIFT) were included and their outcome (at 3 to 10 years of age) was known in 75 families. RESULTS: Prematurity < 32 weeks was highest in the SP pregnancies, with no birth > 37 weeks, and more small-for-dates babies. As of this writing, the neurodevelopmental status was normal or included only a mild deficit (mainly visual corrections) in 82% of SP survivors, 94% of OS survivors, 98% of IVF survivors, all 14 GIFT survivors. Moderate and major deficits were found in one or two siblings of 7 sets of triplets, 5 of which were born < 32 weeks (1 SP, 3 OS, 1 IVF). In all groups, family status was characterized by the need to move, financial problems, maternal exhaustion and parental breakdowns. Five OS mothers, 5 IVF mothers, and one GIFT mother each had one to three subsequent SP pregnancies. In 1997, all families included one to eight children. Because of the cumulative effect of losses, deficits, and other post-natal difficulties, only one of four families had no problems. CONCLUSION: The overall outcome of surviving triplets is good but they are both a prenatal and post-natal hardship for the parents, chiefly the mother. We advocate a more cautious use of OS, no triple implantation at the first IVF, and more social help and guidance for the families during the pregnancy and the first 3 years of life of the triplets.

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The kangaroo-mother method was initiated by colombian pediatricians in 1979. The method is based on a permanent skin to skin contact of low birth weight infants with their mother. It has spread out in many developing countries as an alternative cheap method for the care of low birth weight infants with several advantages: temperature regulation, prolonged breast-feeding, promotion of mother-infant interaction, decreased mortality. The kangaroo method has been adapted in European countries as kangaroo care that consists in daily mother-infant skin to skin contact during few hours. Introducing the incubator in the mother's room is an other derivative of the method which allows prolonged early contact of the mother with her infant. A major interest of these methods is that they favour parent-infant interaction; however this requires qualified and devoted staffs.

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The very early establishment of certain sensory faculties turns the fetus into a being capable of perceiving multiple stimuli. This perceptive capability participates in the many interchanges between the mother and her developing child. The good quality of psychoaffective communication between the mother and her child during pregnancy appears to be decisive for the fetal, perinatal, and later development of the child, especially for an harmonious brain growth. The risks of sensory and sensori-affective overstimulation are considered.

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OBJECTIVE: To assess the physical and neurodevelopmental status of children born after in vitro fertilization (IVF) as well as the family condition. DESIGN: Follow-up study including physical and developmental examination in available families, and/or interviews of parents/pediatricians/teachers/social workers. SETTING: The Port-Royal neonatal intensive care unit and follow-up clinic. SUBJECTS: From 1.1.1987 to 31.12.1992, in 32 single, 71 twin, 28 triple, and one quadruple pregnancies resulting from IVF (total 132), one or more neonates were admitted to the Port-Royal NICU. The outcome is presented for the 99 families followed longer than two years (199 neonates, 166/199 born prematurely). MAIN OUTCOME MEASURES: Neurological sequelae (minor, moderate, major), developmental quotients, school level, behavioral disturbances, family conditions. RESULTS: From 21 singletons (2 deaths, 1 lost), 18 survivors were followed: 17 were normal above 2 years (10 above 3 years went to school), 1 had a severe cerebral palsy with low IQ. From 57 twin pregnancies (7 fetal and 9 neonatal deaths), the 98 survivors were followed: 78 were normal above 2 years (65 above 3 years went to school), 20 had some neuro-developmental deficits (of 14 above 3 years, 12 went to school); 25 families had had or still had problems (deaths and/or anomalies (9 cases) and/or sequelae); 3 mothers were single parents (2 divorces and one split). From 20 triple pregnancies (1 fetal and 3 neonatal deaths), 54 out of 56 survivors were normal above 2 years (33 above 3 years went to school); 3 siblings (1 deaf and 1 with cataract) were put in foster care after severe maternal beating; 2 mothers were single parents (one divorce and one split); 4 mothers had repeated breakdowns; one father tried suicide. From one quadruple pregnancy (one fetal and one neonatal deaths), the 2 survivors were normal above 3 years and went to school. Most sequelae involved very low birthweight babies, in association with a number of sleep and behavioural disturbances. From 98 mothers, 16 had 18 spontaneous pregnancies (11 full-term newborns, 5 miscarriages, 1 extra-uterine pregnancy, 1 abortion) and 3 mothers had another IVF pregnancy (a few others had IVF failures).

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The duration of mechanical ventilation (MV) in very low birthweight infants can sometimes be very prolonged, even in the absence of any respiratory disease. To avoid this, we have developed a double-blind study protocol of the concomitant use of caffeine and doxapram or caffeine and placebo as an aid to early weaning from MV. This protocol necessitated the definition of very precise ventilatory criteria for extubation. Even before the double-blind code has been broken, we can note that the duration of ventilation was very significantly reduced (p < 0.001) from 27.5 days (median; range 1-99) in infants of the retrospective study group to 4 days (median: range 1-34) in the prospective study group (extubation according to strict criteria). This reduction in duration of MV cannot be explained by a difference in the severity of the initial pathology, or by the treatment of some of the infants with doxapram (the difference would not be so marked), but, probably, to the definition of strict criteria concerning extubation.

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This prospective study was designed to assess pulmonary function (functional residual capacity, FRC; dynamic lung compliance, CLdyn; and total pulmonary resistance, RL) at 1 year of corrected age in infants with neonatal respiratory distress syndrome treated with natural porcine surfactant (Curosurf) (n = 13), as compared to nontreated control infants (n = 9). Values from 21 healthy infants of similar age served as reference. We found similar pulmonary dysfunction (decreased CLdyn, elevated RL) in both patient groups. These results suggest that surfactant replacement therapy does not affect pulmonary function at 1 year of age in infants who survive respiratory distress syndrome.

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During the period 1983-1987, 53 neonates (30 boys, 23 girls, mean birth weight 1,438 +/- 317 g, mean gestational age 30 +/- 2 weeks) were found to have cystic periventricular leukomalacias (CPVL) detected by brain ultrasonography. The neuro-developmental follow-up was 3-7 years. Seventeen CPVL were isolated and CPVL were associated with minor peri-intraventricular hemorrhage (0-1 to II-II) in 36 cases. CPVL included 16 minor forms (11 normal children; 2 minor, 3 moderate sequelae), 29 moderate forms (15 normal children; 4 minor, 7 moderate, 3 major sequelae) and 8 major forms (7 major sequelae, one moderate mental retardation without motor deficit). According to reverse analysis, a normal evolution (26 cases) followed CPVL which were sometimes widely, but thinly spread over the ventricles (thickness 1/5-1/3 of the cerebral mantle); minor sequelae (6 cases) were associated with a 1/4-1/3 thickness, moderate sequelae (11 cases) with a 1/3-1/2 thickness, major sequelae (10 cases) with a 1/2-2/3 thickness of CPVL. The thickness of the lesions appeared to be more predictive of sequelae than the sagittal extent, in particular that of the posterior CPVL which played a major role in the severity of sequelae, and mainly in the presence of motor deficits.

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The results obtained with porcine surfactant (Curosurf) administration for the treatment of hyaline membrane disease (HMD) are reported. Thirty premature infants weighing 700 to 2,000 g with severe HMD (mechanical ventilation and oxygen requirement (FiO2) greater than 60% were randomly allocated at 2 to 15 hours postnatal age. Eight of the 30 patients included in this group participated in a multicenter european trial. The fifteen infants with mean gestational age (GA) of 29.5 weeks included in the treatment group (T), were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group (C). Infants in the T group showed an immediate, dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour. This significant improvement in favor of T group (p less than 0.005) persisted for 2 days when control infants began to recover. This improvement in oxygenation allowed a significant decrease of FiO2 (p less than 0.005) and mean airway pressure (p less than 0.01) in the T group within 1 hour and up till the second day. Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified. However the tendency was towards decreased respiratory morbidity. The discussion will consider the value of multiple doses.

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The authors analyse the results of the different trials of exogenous surfactants for the treatment of hyaline membrane disease. Whether artificial and used for prevention, or of human or animal origin and used for prevention or treatment, exogenous surfactants appear to improve the survival of premature infants. The improvement does not occur at the expense of increased morbidity. Indeed, there seems to be no increase in the frequency of patent ductus arteriosus, broncho-pulmonary dysplasia appears to be less frequent, and results on the effects of the frequency of intraventricular hemorrhage are contradictory. Current trials using new therapeutic schemes with multiple doses may further improve the protective effects of exogenous surfactants in premature infants.

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Pulmonary function was evaluated in both infancy and childhood in the same 19 prematurely born infants, who required mechanical ventilation (MV) during the neonatal period. Results of our patients were compared with those of control subjects. Upon first evaluation, we found that lung resistance (RL) was significantly elevated (24.85 +/- 6.06 vs. 17.77 +/- 2.39 cmH2O/L/s; P less than 0.01). The mean value of dynamic lung compliance (CLdyn) was low, but the difference compared to controls did not reach significance. From infancy to childhood, elevated RL persisted (9.33 +/- 2.51 vs. 6.52 +/- 1.52 cm H2O/L/s; P less than 0.01), and the decrease of CLdyn became significant (46.86 +/- 12.84 vs. 59.34 +/- 15.68 mL/cmH2O; P less than 0.05). In addition, maximum flow at functional residual capacity was significantly decreased (0.824 +/- 0.284 vs. 1.215 +/- 0.358 L/s; P less than 0.01); whereas pulmonary diffusing capacity for carbon monoxide was similar in the patients (7.62 +/- 2.16 mL/min/mm Hg) and in the controls (8.38 +/- 1.6). Pulmonary dysfunction following premature birth, respiratory distress, and prolonged MV may not resolve from infancy to childhood.

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Acute imbalance between elastase and alpha-1-proteinase inhibitor (alpha 1Pi) may contribute to the development of bronchopulmonary dysplasia (BPD). The question of whether such an imbalance persists in BPD infants still requiring mechanical ventilation after 4 wk of life has not been previously addressed. We studied 14 infants still on mechanical ventilation at 4 wk of age: nine had BPD and five did not. Weekly (4 to 9 wk) serum and bronchoalveolar lavage (BAL) specimens were taken. alpha 1Pi and alpha-2-macroglobulin were measured in serum and BAL by immunoturbidimetric assay. BAL elastase activity was measured by cleavage of a synthetic substrate and expressed as ng of porcine pancreatic elastase equivalent. Infants with BPD had higher levels of serum alpha 1Pi and alpha-2-macroglobulin than those without BPD. In contrast, the corresponding BAL levels were either similar or even decreased (alpha 1Pi). Moreover, there was a 3-fold increase in elastase-1Pi imbalance expressed as the BAL ng of porcine pancreatic elastase equivalent/2 alpha 1Pi ratio. The role of nosocomial infections was evident in a subgroup of 11 infected BAL aspirates in BPD infants. In such cases we found a 3-fold increase in the BAL ng of porcine pancreatic elastase equivalent/alpha 1Pi ratio as compared to 35 noninfected BAL in BPD infants. These data suggest a persistent alveolitis with imbalance between elastase and proteinase inhibitors in prolonged severe BPD. Such an imbalance is, in part, explained by a local destruction and/or inactivation of alpha 1Pi. Our results also emphasize the increase in proteolysis with nosocomial pneumonia.

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After a brief historical recall, this review states the needs for an accurate diagnosis of the neonatal respiratory distress syndrome (RDS). The clinical features consist of disturbances of respiratory rate, grunting, intercostal retractions, and cyanosis, but early mechanical ventilation tends to suppress most of them. Laboratory findings include hypoxemia, hypercapnia, and mixed acidosis. Positive radiological diagnosis remains an important criterion but early ventilation with positive end-expiratory pressure has made grading obsolete. The biochemical diagnosis addresses the basic lung surfactant deficiency, by determination of the lecithin/sphingomyelin ratio and phosphatidylglycerol ("modified lung profile") in lung effluents at birth. If clinical and radiological diagnosis remains adequate for daily practice and epidemiological studies, biochemical diagnosis should be mandatory for therapeutic trials. However, the problem of atypical RDS in very low birth weight infants has not been totally solved. RDS has now been known for more than 80 years; yet its diagnosis is still a matter of controversy.

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