Liisa Lehtonen

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997

Objective. Increasing survival of extremely low birth weight (ELBW; birth weight <1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. Methods. Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996–1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at <27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence–Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. Results. The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at <27 GW). The mean full-scale IQ of the assessed children was 96 ± 19 and in children of GW <27 was 94 ± 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. Conclusions. Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

No improvement in outcome of nationwide extremely low birth weight infant populations between 1996-1997 and 1999-2000

OBJECTIVE. Our goal was to investigate whether outcome in extremely low birth weight infants changes over time in Finland. PATIENTS AND METHODS. All infants with a birth weight <1000 g born in Finland in 1996–1997 and 1999–2000 were included in the study. Perinatal and follow-up data were collected in a national extremely low birth weight infant research register. Data concerning cerebral palsy and visual impairment were obtained from hospitals, the national discharge, and visual impairment registers. RESULTS. A total of 529 and 511 extremely low birth weight infants were born during 1996–1997 and 1999–2000. No changes were detected in prenatal, perinatal, neonatal, and postneonatal mortality rates between the periods. The survival rates including stillborn infants were 40% and 44%. The incidence of respiratory distress syndrome and septicemia increased from 1996–1997 to 1999–2000 (75% vs 83% and 23% vs 31%). The overall incidence of intraventricular hemorrhage increased (29% vs 37%), but the incidence of intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did not change. Mortality remained higher in 1 university hospital area during both periods compared with the other 4 areas, but no regional differences in morbidity were detected during the later period. CONCLUSIONS. No significant changes were detected in birth or mortality rate in extremely low birth weight infants born in Finland during the late 1990s, but some neonatal morbidities seemed to increase. Regional differences in mortality were detected in both cohorts. Repeated long-term follow-up studies on geographically defined very preterm infant cohorts are needed for establishing reliable outcome data of current perinatal care. Regional differences warrant thorough audits to assess causalities.

Closeness and separation in neonatal intensive care

In this paper, we highlight the need for acknowledging the importance and impact of both physical and emotional closeness between the preterm infant and parent in the neonatal intensive care unit. Physical closeness refers to being spatially close and emotional closeness to parental feelings of being emotionally connected to the infant (experiencing feelings of love, warmth and affection). Through consideration of the literature in this area, we outline some of the reasons why physical closeness and emotional closeness are crucial to the physical, emotional and social well‐being of both the infant and the parent. These include positive effects on infant brain development, parent psychological well‐being and on the parent–infant relationship. The influence of the neonatal unit environment and culture on physical and emotional closeness is also discussed.

The effects of preterm birth on mother–infant interaction and attachment during the infant's first two years

Abstract  Objective. Early mother–infant relationships in preterm populations were evaluated in the context of a systematic review of the literature. Design and setting. A systematic search of three electronic databases (PsychINFO, PubMed and Cochrane Library) was undertaken. Three studies of maternal attachment, 18 studies of mother–preterm infant interaction and eight studies of infant attachment were included. Studies of preterm infant attachment were also evaluated using a meta‐analysis. Results. Studies of mother–preterm infant interactions showed that the differences in maternal interaction behavior between mothers of preterm infants and mothers of full‐term infants seem to be most evident during the first six months of life. Differences in the preterm infants interaction behavior seem also to continue for six months after birth. However, five of 18 studies showed an equal or even higher quality of mother–infant interaction in groups of preterm compared to groups of full‐term infants. Studies of maternal and infant attachment indicated that preterm infants and their mothers are not at higher risk of insecure attachment than full‐term infants and their mothers. Conclusions. The mother–preterm infant relationship is complex, and some relational patterns forecast greater psychological risk than others. It is important to decrease maternal stress and early separation in every possible way during hospitalization as well as after discharge.

Maternal depression is associated with mother-infant interaction in preterm infants.

Aim: The purpose of this study was to assess the prevalence and the background factors of maternal depressive symptoms and their relation to the quality of mother–infant interaction in a group of preterm infants and their mothers.

Risk of Autism Spectrum Disorders in Low Birth Weight and Small for Gestational Age Infants

OBJECTIVE To examine the relationship between birth weight, gestational age, small for gestational age (SGA), and 3 of the most common autism spectrum disorder (ASD) subtypes. STUDY DESIGN In this population-based case-control study conducted in Finland, 4713 cases born between 1987 and 2005 with International Classification of Diseases-diagnoses of childhood autism, Asperger syndrome, or pervasive developmental disorder (PDD), were ascertained from the Finnish Hospital Discharge Register. Four controls, individually matched on sex, date of birth, and place of birth, were selected from the Finnish Medical Birth Register for each case. Conditional logistic regression models were used to assess whether birth weight and gestational age information predicted ASD after controlling for maternal age, parity, smoking during pregnancy, and psychiatric history, as well as for infants major congenital anomalies. RESULTS Very low (<1500 g) and moderately low (<2500 g) birth weight, very low gestational age (less than 32 weeks), and SGA increased risk of childhood autism (adjusted OR 3.05, 95% CI 1.4-6.5; 1.57, 1.1-2.3; 2.51, 1.3-5.0; and 1.72, 1.1-2.6, respectively). Very low and moderately low birth weight, very low gestational age, and SGA were also associated with increase in PDD risk (OR 3.44, 95% CI 1.9-6.3; 1.81, 1.4-2.4; 2.46, 1.4-2.3; and 2.24, 1.7-3.0, respectively). No associations were found between the perinatal characteristics and Asperger syndrome. The increased risks persisted after controlling for selected potential confounders. CONCLUSIONS The finding that low birth weight, prematurity, and SGA were related to childhood autism and PDD but not to Asperger syndrome suggests that prenatal factors related to these exposures may differ for these ASD subtypes, which may have preventive implications.

Oral Glucose and Parental Holding Preferable to Opioid in Pain Management in Preterm Infants

ObjectivesThe purpose of this study was to compare the effectiveness of “facilitated tucking by parents” (FTP) in which a parent holds by her hands the infant in a side-lying flexed position offering support and skin contact, oral glucose, opioid (oxycodone), and placebo (oral water) in the context of heel stick and pharyngeal suctioning in very preterm infants. We hypothesized that nonpharmacologic methods equal the pharmacologic method and are superior to placebo in pain management. MethodsA prospective randomized placebo-controlled crossover trial. The study patients (n=20) were born at a mean gestational age of 28+1 weeks and were studied at postconceptional age of 28 to 32 weeks. Pain measurements with Premature Infant Pain Profile and Neonatal Infant Pain Scale covered the first 30 seconds after the beginning of the painful stimulus. ResultsPremature Infant Pain Profile scores were significantly lower with oral glucose (mean: 4.85±1.73, P≤0.001) and FTP (mean: 5.20±1.70, P=0.004) when compared with placebo (mean: 7.05±2.16) after heel stick. During pharyngeal suctioning, the scores were lowest with oral glucose (mean: 11.05±2.31, P=0.014) and FTP (mean: 11.25±2.47, P=0.034) compared with placebo (mean: 12.40±2.06). Opioid equaled placebo in both procedures. Neonatal Infant Pain Scale scores were significantly lower with FTP (P≤0.001) and opioid (P=0.018) after heel stick, and during pharyngeal suctioning with FTP (P=0.001) compared with placebo. We found significantly more short-term adverse effects per administration with oral glucose (21.25%) and oral water (12.5%) compared with opioid (5%) or FTP (5%). DiscussionOur study demonstrated that FTP is not just equal, but preferable to other pain management methods when both efficacy and safety are considered.

Randomized Trial of a Single Repeat Dose of Prenatal Betamethasone Treatment in Imminent Preterm Birth

BACKGROUND. A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial. METHODS. Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4). RESULTS. A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age-adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates. CONCLUSIONS. According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies.

Intestinal microflora in colicky and noncolicky infants: bacterial cultures and gas-liquid chromatography.

Summary: To find out whether intestinal microflora in colicky infants is different from that in noncolicky controls, stool samples were collected from colicky infants during colic (n = 55) and at the age of 3 months (n = 46) and compared with samples from age-matched controls (n = 49 and n = 45, respectively). The samples were cultured on several selective and unselective aerobic and anaerobic culture agars, and gas-liquid chromatography of bacterial cellular fatty acids was used to produce fatty-acid profiles of the stool samples. In quantitative bacterial cultures, no differences were found between the colicky and control groups in the amounts of each bacterium. The colicky infants were more frequently colonized with Clostridium difficile during the time of colic than were the age-matched controls. This difference disappeared by age 3 months. The fatty-acid profiles did not differ between the colicky and control groups as a whole at the time of colicky symptoms. At age 3 months, a difference in fatty-acid profiles was found between the colicky infants who had suffered from severe colic and the control infants. The fatty-acid profiles were also influenced by the age of the infant, the mode of delivery, antimicrobial drugs taken by the mother during delivery, and breast-feeding and type of feeding. In conclusion, no difference in intestinal microflora was found between the colicky infants at the time of colic and the controls. However, a difference in bacterial cellular fatty-acid profiles at the age of 3 months was found that correlated with severe infantile colic. This difference may contribute to the cause(s) of colic, or it may be secondary to the colic, which may influence the microbial environment of the intestine.

Parenteral plant sterols and intestinal failure-associated liver disease in neonates.

Objectives: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure–associated liver disease (IFALD) compared with children. Methods: We recruited 28 neonates (mean age 50 days, range 28–126) and 11 children (6.9 y, 2.1–16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n = 10) and children (n = 22) served as controls. Results: IFALD occurred more frequently among neonates (63%) than children (27%; P < 0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P < 0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P < 0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r = 0.472–0.636, P < 0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r = 0.529–0.688, P < 0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P < 0.05). Conclusions: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.