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Metabolic Bone Disease In Preterm Infants

Department of Pediatric Propedeutics and Metabolic Bone Diseases, Medical University of Łódź, Poland

Archives of Perinatal Medicine 15(4), 230-232, 2009 CASE REPORT
Metabolic bone disease in preterm infants: two cases report

ELŻBIETA JAKUBOWSKA-PIETKIEWICZ, ANNA SZCZEPANIAK-KUBAT,
DANUTA CHLEBNA-SOKÓŁ

Abstract

Premature infants are at risk of abnormal skeletal mineralization and low bone mass.We report two cases of
osteopenia in preterm babies. The patient’s medical history as well as diagnostic procedures assessing skeletal
status (biochemical tests and dual energy X-ray absorptiometry – DXA) were presented. The study also aims to
discuss risk factors for metabolic bone disease in these cases

Introduction
In the last trimester of pregnancy, intensive growth
and mineralization of bony tissue expressed by high calcium
and phosphorus retention occurred. Thus, premature
birth may lead to abnormal mineralization and low
bone mass. Additionally, prolonged immobilization of
a newborn, pharmacotherapy as well as an insufficient
supply of calcium, phosphorus and protein in the diet
may intensify bone metabolism disorder [1, 2].
Osteopenia of prematurity occurs in 20-30% of children
with a birth weight below 1500 g and in the half of
those below 1000 g [3].

 

For full PDF paper please see Source:

http://www.ptmp.pl/archives/apm/15-4/APM154-7-Jakubowska.pdf

Metabolic Bone Disease In Preterm Newborn: An Update On Nutritional Issues

Authors:

Valentina Bozzetti

Paolo Tagliabue

Abstract:

Osteopenia, a condition characterised by a reduction in bone mineral content, is a common disease of preterm babies between the tenth and sixteenth week of life. Prematurely born infants are deprived of the intrauterine supply of minerals affecting bone mineralization.
The aetiology is multifactorial: inadequate nutrients intake (calcium, phosphorus and vitamin D), a prolonged period of total parenteral nutrition, immobilisation and the intake of some drugs.
The diagnosis of metabolic bone disease is done by biochemical analysis: low serum levels of phosphorus and high levels of alkaline phosphatase are suggestive of metabolic bone disease. The disease can remain clinically silent or presents with symptoms and signs of rachitism depending on the severity of bone demineralisation.
An early nutritional intervention can reduce both the prevalence and the severity of osteopenia.
This article reviews the pathophysiology of foetal and neonatal bone metabolism, focuses on the nutrient requirements of premature babies and on the ways to early detect and treat osteopenia.

Background:

The continuous advances in intensive care of preterm newborns have led to a progressive decline of mortality in Institutions where facilities and expertise for respiratory resuscitation and respiratory distress syndrome are available. Infant mortality dropped among all races between 1980 and 2000. The survival rate depends on the gestational age of the newborn; actually the survival rates for very low birth weight (VLBW) are the following: for those weighing 501 – 750 g is 56% and for the ones above 750 is 88% [1]. However, the success in the survival achieved through an aggressive intensive care is not always paralleled by a subsequent fully healthy development of the newborn.
Among the common conditions of morbidity due to the prematurity (cerebral impairment, bronchopulmonary dysplasia, growth failure, retinopathy…) a growing interest is focusing now on the metabolic bone disease of the prematurity (MBD), also called osteopenia of prematurity.
This condition is characterised by a reduction in bone mineral content (osteopenia), with or without rachitic changes, and is caused by several nutritional and biomechanical factors.
An inadequate supply of nutrients (vitamin D, calcium and phosphorus), a prolonged period of total parenteral nutrition, immobilisation and the intake of some drugs are the main factors involved in the pathogenesis of osteopenia [2].
The MBD usually occurs between tenth and sixteenth week of life, but it may remain silent until severe demineralisation (a reduction of BMD of 20 – 40%) occurs.
The clinical picture is various, ranging from a totally silent condition to a clinical picture of overt rickets, with multiple fractures and other alterations, when the demineralisation is severe.
The purpose of this review is to focus on the recent advances in the understanding of the bone tissue metabolism and on the nutritional approach to prevent and to treat the MBD.

Magnitude Of The Problem:

The prevalence of MBD varies depending on gestational age, birthweight and kind of alimentation.
It occurs in up to 55% of babies born with weight under 1000 g [3] and 23% of infants weighing < 1500 g at birth [4] and it is especially frequent in babies under 28 weeks of gestation. The prevalence is 40% in premature infants who are breastfed, in contrast to 16% of those fed with a formula designed for preterm infants and supplemented with calcium and phosphorus [5,6].
Preterm infants with a complicated medical course and delayed nutrition are also at high risk for MBD. Actually in western countries there is a trend of decrease of gestational age and birthweight, so the frequency of the MBD is expected to further increase.

Homeostasis of calcium -phosphorus

The homeostasis of calcium, phosphorus and magnesium is fundamental for structural matrix of the bone.
Calcium and phosphate represent the major inorganic constituents of bone. The highest amount of calcium (99%) and of phosphorus (80%) of the whole body is in the bone as microcrystalline apatite.
Only 1% of the total body calcium is within the extracellular fluids and soft tissues. About the 50% of total serum calcium is in the ionised form and represents the biologically active part. A further 8–10% is bounded to organic and inorganic acid and the remaining percentage of calcium is protein-bound (80% to albumin, 20% to globulin).
The formation of the apatite takes place if calcium and phosphorus are simultaneously available in optimal proportions.
Also magnesium is part of the bone matrix and the 60% of total body magnesium is in the bone.
Calcium and phosphorus homeostasis is a function of hormones, vitamin D and dietary intake, and depends on the intestinal absorption, skeletal accretion and reabsorption, and urinary excretion. [7]
Parathyroid hormone (PTH) is synthesised and secreted from the parathyroid glands in response to a reduction of serum level of ionised calcium. PTH regulates mineral metabolism and skeletal homeostasis through its action on target cells in bone and kidneys. It stimulates the reabsorption of calcium and excretion of phosphorus in the kidney and bone reabsorption of calcium. PTH also is able to activate the synthesis of calcitriol via stimulation of renal 25 (OH) D3-1-alpha-hydroxylase activities.
In its active form, 1, 25(OH) 2 vitamin D, stimulates the renal reabsorption of calcium and phosphorus. The synthesis of calcitriol is inhibited by elevated serum levels of calcium and phosphorus.
The combined actions of PTH and calcitriol maintain the adequate concentration of calcium in the extracellular fluids.
Kidneys contribute to maintain homeostasis of calcium; urinary calcium is one third derived from diet and the remaining from body stores, mostly bone.
Diuretics, as furosemide, increase renal calcium excretion.

Prenatal bone physiology

The amounts of minerals required for a correct accretion of the skeleton are widely different depending on the age of the babies.
The period of greater skeletal development is during the intrauterine life and specifically during the last trimester. The bone volume increases significantly with gestational age and the high net bone formation activity is mainly due to modelling, with a rapidly increasing trabecular thickness (the trabecular thickening rate being approximately 240 times faster in the foetus than in the children).
The mineralization process is determined by synthesis of the organic bone matrix by osteoblasts (osteoid) onto which calcium and phosphate salts are deposited. This process increases exponentially between 24 and 37 weeks of gestation, reaching the 80% of mineral accretion in the third trimester [8].
During gestation the developing fetus receives supplies of energy, protein and mineral for adequate growth (1.2 cm/week) and bone development.
At term the newborn skeleton has a high physical density (expressed as bone mass divided by bone volume).
The foetal accretion of calcium and phosphate during the last three months of gestation is about 20 g and 10 g respectively, which represents accretion rates of 100–120 mg/kg/day for calcium and 50–65 mg/kg/day for phosphate [9].
A very important role in skeletal accretion of the foetus is played by the placenta. In fact the transfer of calcium from the mother to the foetus through the placenta occurs via an active transport done by the calcium pump in the basal membrane [10]. There is a 1:4 maternal to foetal calcium gradient [11].
Moreover, the placenta is able to convert vitamin D to 1,25-dihydrocholecalciferol which is fundamental for transferring phosphate to the foetus [12].
The foetus is maintained hypercalcemic in a high calcitonin and estrogen environment which promotes the modelling/remodelling ratio in favour of modelling and thus increasing the endocortical bone [13].
As a result, infants born prematurely will be deprived of the intrauterine supply of calcium and phosphorus affecting bone mineralization.
It is well known that a chronic damage to the placenta may alter the phosphate transport; this explains why babies with intrauterine growth restriction may be osteopenic.
Demineralization is also observed in infants born from mother with chorioamniositis and placental infection [14].
Maternal dietary intake of calcium is a factor implied in foetal bone accretion. A supplement of calcium (2 g from before 22 weeks of gestation) to women with a low dietary calcium intake resulted in higher bone mineral content (BMC) of the total body in infants born at term [15].
After birth the physical density of term newborns bones decreases by 30% in the first 6 months of life [13]. This is mostly due to an enlargement of the marrow cavity size, which occurs faster than the increase in the cross-sectional area of the bone cortex [16]. In term infants these postnatal changes are not accompanied by an increase in bone fragility and occur because bone is exposed to different conditions before and after birth.
First, there are important changes of hormonal environment: the reduction of maternal estrogens [17] and a postnatal increase of PTH level mainly due to a reduction of the calcium supply by the placenta [18].
As the serum calcium levels falls in the first day of life, PTH secretion is stimulated. During this transition the response of the parathyroid gland to falling levels of ionised calcium is blunted, as emphasized in a recent review article [19]. This finally results in a physiological nadir in neonatal serum calcium levels within the first 48 hours of life. Of note, PTH level is still within the normal range for term babies or adult, but represents a decrease from foetal levels.
Many factors affect calcium absorption including the maternal vitamin D status, solubility and bioavailability of calcium salts, quality and quantity of calcium, amount and type of lipids and, obviously, gut function.
Calcium absorption from the intestine occurs both passively and through a vitamin-D dependent active transport mechanism. In a newly born preterm the low mineral content of human milk associated with a poorly efficient absorption of the developing gut determine a net reduction of calcium and phosphorus supply.
Absorption of phosphorus takes place in the jejunum and depends on the dietary intake. The phosphorus supply regulates calcium absorption and retention: the higher is the phosphorus content of the diet, the higher is the calcium retention. However, an excessive amount of one decreases the absorption of the other.
Moreover, while in utero fetus experiments mechanical stimulation by kicking against the uterine wall, this kind of training is missing during the extrauterine life since preterm babies usually stay in the incubator [20,21]. Inactivity due to immobilisation stimulates bone reabsorption by osteoclasts and urinary calcium excretion; furthermore the reduced muscle activity prevents the addition of new bone tissue [22]. Conditio sine qua non for the physical activity to be beneficial is that an adequate mineral intake is guaranteed [23].
The figure figure11 shows that during the third trimester of gestation, bone mineral apparent density (BMAD) increases at a faster rate in utero (term infants) than ex utero (preterm infants) according to gestational age.
Physiological evolution of DEXA apparent bone mineral density during the last trimester of gestation (filled squares) and during the first year of life in healthy term infants (upper triangles) compared to that observed in preterm infants (open squares
BMAD is an estimation of volumetric BMD (g/cm3) calculated as bone mineral content/bone area (BMC/BA). The figure figure11 also shows that there is a sharp reduction in BMAD in neonatal age followed by a stabilization that lasts all the first year of life (“black triangles”). A similar event occurs in preterm babies: from birth to the term, mineral retention sharply diminishes comparing with the foetal life, while the skeletal growth remains high. This leads to a reduction of bone density (“white squares”). A catch up mineralization occurs after discharge of VLBW so BMC spontaneously improves (“white rhombs”).
Among the other pathogenic factors, also problems related to inadequate supply of calcium to babies, which require parenteral nutrition and interference of several drugs, may contribute to determine preterm osteopenia with an increasing risk of bones fractures.
The drugs mostly implied in pathogenesis of MBD include steroids, methylxanthines and diuretics. They stimulate osteoclasts activation, decrease calcium absorption, reduce osteoblasts proliferation and increase calcium renal excretion and hence increase the risk of poor bone mineralization [24-26].

Neonatal mineral requirements

The requirements of calcium and phosphorus are based on demands for matching intrauterine bone mineral accretion rates.
Supplying calcium and phosphorus in parenteral nutrition is a challenge because of limited solubility of these two minerals. Calcium and phosphorus’s solubility in nutrition admixtures depends on temperature, type and concentration of aminoacid, glucose concentration, pH, type and concentration of calcium salts, and presence of lipid and so on…
In parenteral nutrition calcium is administered as inorganic salt and phosphorus may be administered as inorganic sodium and potassium phosphate or sodium-glucose phosphate or glycerolphosphate, which are quite soluble in water.
The addition of cystein to lower pH of the parenteral admixtures improves the solubility of calcium and phosphorus.
For all such reasons it is not possible to supply these minerals according to the physiologic requirements of the preterm to reach an adequate bone mineralization.
In the transition period, most of VLBW neonates receive full or partial parenteral nutrition with the goal to maintain normal levels of calcium and phosphorus. Hypocalcaemia, in fact, is a common event during the first days of life because of the sharp decrease of the calcium supply by the placenta and the delayed release of PTH due to the immature response of the parathyroid glands.
Parenteral administration of 50–75 mg of calcium/kg/day can prevent early neonatal hypocalcaemia in preterm infants.
Through the parenteral administration of calcium and phosphorus (40–70 mg/kg/day and of 25–45 mg/kg/day respectively) it is possible to achieve 60 – 70% of intrauterine mineralization [27]. The best calcium to phosphorus ratio for bone mineralization is 1.7:1 [28-30].
In preterm babies receiving parenteral nutrition only limited amounts of vitamin D are required since calcium is given by vein and there is no need of calcitriol to facilitate the intestinal uptake.
Moreover only the parent compound needs to be administered since the preterm infant is able to hydroxylate the inactive form to the active one since the 24th week of gestation. It is now generally accepted the daily recommended dose of vitamin D is 400 U.I./day [18].
For the transitional period, when infants are weaned from parenteral nutrition to the enteral one, the aim usually is to maintain an adequate serum level of calcium and phosphorus. However the serum level of calcium is not a good marker of adequacy of calcium intake since the level is maintained stable at the expense of the bone. Therefore the clinicians should be aware that a normal serum level of both calcium and phosphorus are not guarantee for an adequate whole body accretion as in intrauterine life.
The enteral administration of calcium is fraught with many problems as regards the calcium bioavailability. Vomiting, large gastric aspirates, constipation and abdominal distension are quite common in preterm babies and the gut absorption capacity is impaired due to the immaturity of the gastrointestinal mucosa.
Calcium absorption depends on vitamin D status, solubility of calcium salts, quality and quantity of lipid intake. Moreover, in preterm babies, vitamin D demands are influenced by body contents at birth which depends on the duration of gestation and maternal vitamin status.
Current estimates of requirements for calcium, phosphorus and vitamin D in growing premature infants vary among international sources of recommendations [31-34] (Table 1).

Minerals and vitamin D recommended intakes in growing preterm infants.

The human milk content is inadequate for preterm requirements since the content of calcium and phosphorus in preterm human milk is 31 mg/100 kcal and 20 mg/100 kcal [18] while the Life Science Research Office [31] suggests, for premature formulas, a dose approximately 4–6 times higher (123 to 185 mg Ca/100 kcal and 80 to 110 mg P/100 kcal). Even when VLBW are fed at high feeding volumes (180–200 mL/Kg), assuming calcium and phosphorus absorption of 70% and 80% respectively, this would provide only one-third of the in utero level of absorbed calcium and phosphorus [6]. Formula milk is richer in calcium and phosphorus than human one, but bioavailability is quite different. In formula fed infants, calcium absorption is usually less than with human milk, ranging from 35 to 60% of the intake. Hence the human milk intake has to be promoted, but a fortification with mineral and protein fortifier is necessary to achieve adequate nutrient intake.
With the current human milk fortifiers, containing highly soluble calcium glycerolphosphate, calcium retention reaches a level of 90 mg/kg/day (88% of the overall intake).
However the new human milk fortifiers available in the market still do not allow intakes of calcium comparable with the values achieved during the last trimester of gestation (100–120 mg/kg/day) which are considered the target mineral accretion for preterm infants, nevertheless the use of multinutrient fortification of human milk for premature infants is currently recommended.
A Cochrane systematic review and metaanalysis of human milk fortifiers, which however included studies on children who were not extremely preterm (the class at major risk) stated that the effects on bone mineralization were not conclusive [35].
Finally, it must be noted that high calcium supplementation of milk is not well tolerated; it is associated with high faecal calcium, prolonged gastrointestinal transit time and impaired fat absorption. All these effects are potential risk factors for developing necrotizing enterocolitis.

Clinical features and diagnosis

MBD remains silent until a severe demineralisation occurs. The most evident clinical findings of osteopenia are deformity of the skull (diastasis of the suture, enlargement of the sagittal fontanelle and frontal bosses, craniotabe), thickening of the chondrocostal junctions and of the wrists, rib and long bones fractures. Softening and/or fractures of the ribs can cause pulmonary changes and respiratory distress, typically between 5 and 11 weeks of age [36].
Diagnosis of osteopenia is mainly done by serum analysis. Biochemically osteopenia is characterised by low serum levels of phosphorus and by an increase in serum levels of alkaline phosphatase that can reach values 5 times higher than the upper reference range used for adults [37]. It is useful dosing the isoenzimes of alkaline phosphatase since this enzyme is synthetised also by the liver and by the gut.
Backstrom and colleagues suggested that serum alkaline phosphatase levels higher than 900 U.I/l associated with a serum phosphate level lower than 1.8 mmol/l have a diagnostic sensitivity of 100% and specificity of 70% [38]. However the opinions in literature about the reliability of alkaline phosphatase to predict the status of bone mineralization are still conflicting [39,40]
Serum level of calcium is usually within the normal range due to effects of PTH on the bone. Low concentrations of calcium and phosphorus in the urine suggest an inadequate intake. This is manly due by an increase of the tubular reabsorption of phosphate because of the low dietary intake and by an increase of PTH level that stimulates the reabsorption of calcium. Markers of nutritional status should be assessed baseline, and then weekly during the initial phase; once the newborn is stable, assessment must be done at the starting of total enteral nutrition and successively every 2–3 weeks. If MBD is diagnosed and nutritional supplementation is started, a periodic assessment of laboratory data is necessary to evaluate the response to treatment also when babies are discharged from hospital. The key clinical goal is to maintain normocalcemia and normophosphatemia and to avoid an excessive calciuria.
Once levels of ALP, calcium and phosphorus normalize, serum analysis can be performed monthly up to 6 months of age and then every 3 months.
X-rays examination may show fractures, thin bones and other alterations as reduction of thickness of the cortical, enlargement of the epiphysis, irregular border between growth cartilage and bony metaphysis [41].
Dual energy X-ray absorbitometry (DEXA) is able to determine the bone mass content of neonates and can predict the risk of fractures [39,42] since it is sensitive in detecting small changes in BMC and BMD. Its use is now validated in neonates both term and preterm ones.
DEXA reflects most accurately the state of bone mineralization in preterm infants [43] but the examination involves radiations for the baby and the device is not portable.
Quantitative ultrasound is simpler than DEXA and is non-invasive; it can be used bedside without moving the baby. Reference values are now available for infants. Quantitative ultrasound gives information about structure of the bone and about bone density [44].
Osteopenia has a good prognosis since the disease is self-resolving, provided that calcium, phosphates and vitamin D are appropriately administered to the babies.
It is still controversial the need for high calcium and phosphorus intakes in preterm infants after hospital discharge. Few data are available about the optimal length, quantity and methods of providing supplemental minerals for preterm infants who are in stable growth.
There are studies that show increased bone mineral mass in infants who receive formulas containing more minerals that the traditional ones up to 9 months [45,46].
It has been shown, with studies assessing bone mineralization with quantitative ultrasound and DEXA, that preterm infants show a catch-up mineralization for the first year of life. There is no difference in late childhood of bone mineralization between term and ex-preterm infants [47] even though the biochemical evidence of metabolic bone disease during the neonatal period may have a long-term stunting effect which continues up to 12 years later. A recent study published on Journal of Perinatology [48] stated that children who were born prematurely with birth weights less than 1.5 kg tend to be significantly smaller for age and have lower lumbar spinal bone mineral content and density compared with children born at term gestation.
The long duration of this complication provides further rationale for implementing any practice that can prevent this condition [49].
In the case of BMD of prematurity nutrition is both therapy and prevention. An adequate intake of minerals and of vitamin D, with breast milk fortifier or formula with a content of minerals suitable for preterm infant’s requirements, are necessary for a correct bone mineralization.
A regular physical stimulation, when the preterm infant is clinically stable and is receiving adequate doses of calcium, phosphate and vitamin D, should also be included in the standard preventive approach.

Conclusion

An adequate nutritional intake of calcium, phosphorus and vitamin D and passive physical exercise may prevent abnormal bone-remodelling activity during first weeks of life and may optimize growth potential of preterm infants. It is important to recognize the biochemical signs of osteopenia in an early stage in order to be able to precociously implement the dietary intake and reduce the risk of bones fractures. The determination of alkaline phosphatase and of phosphoraemia seems to be useful in assessing the risk of metabolic bone disease and serum analysis need to be performed periodically in order to assess response to nutritional treatment. Through DEXA and quantitative ultrasound it is also possible to determine the state of bone mineralization and therefore to plan a nutritional intervention.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

VB and PT equally contributed at the article, analyzing the literature and writing the paper. All authors read and approved the final manuscript.

Acknowledgements

We are grateful to Prof. G. Weber, University Vita-Salute, San Raffaele Scientific Institute of Milan, Italy, for her helpful advice.

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  • Bruton JA, Bayleys HS, Atkinson SA. Validation and application of dual-energy X-ray absorpiometry tto measure bone mass and body composition in small infants. Am J Clin Nutr. 1993;58:839–45. [PubMed]
  • Rubinacci A, Moro GE, Bohem G, De Terlizzi F, Moro GL, Cadossi R. Quantitative ultrasound for the assessment of osteopenia in preterm infants. Eur J Endocrinol. 2003;149:307–15. doi: 10.1530/eje.0.1490307. [PubMed] [Cross Ref]
  • Kurl S, Heinonen K, Lansimies E. Pre- and post-discharge feeding of very preterm infants: impact on growth and bone mineralization. Clin Physiol Funct Imaging. 2003;23:182–9. doi: 10.1046/j.1475-097X.2003.00493.x. [PubMed] [Cross Ref]
  • Lapillonne A, Salle BL, Glorieux FH, Claris O. Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term. Am J Clin Nutr. 2004;80:1595–603. [PubMed]
  • Fewtrell MS, Prentice A, Jones SC, Bishop NJ, Stirling D, Buffenstein R, Lunt M, Cole TJ, Lucas A. Bone mineralization and turnover in preterm infants at 8–12 years of age: the effect of early diet. J Bone Miner Res. 1999;14:810–20. doi: 10.1359/jbmr.1999.14.5.810. [PubMed] [Cross Ref]
  • Chang JM, Armstrong C, Moyer-Mileur L, Hoff C. Growth and bone mineralization in children born prematurely. J Perinatol. 2008;28:619–23. doi: 10.1038/jp.2008.59. [PubMed] [Cross Ref]
  • Fewtrell MS, Cole TJ, Bishop NJ, Lucas A. Neonatal factors predicting childhood height in preterm infants: evidence for a persisting effect of early metabolic bone disease? J Pediatr. 2000;137:668–73. doi: 10.1067/mpd.2000.108953. [PubMed] [Cross Ref]

Source:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729305/

Behavior Of A Premature Child

Preemie Personality – Dr. Mary Shirley (1939)


A behavior syndrome characterizing the prematurely-born child from Dr. Mary Shirley of the Harvard Center for Child Health and Development.

By Helen Harrison


Part 1.

These observations come from Dr. Mary Shirley of the Harvard Center for Child Health and Development and were published in 1939 in Child Development. The preemies weighed below 5 pounds and were less than 8 1/2 months gestation. They were examined between the ages of 6 months and 30 months.

Here were some of the results:

Sensory acuity:

“In auditory sensitivity the premature child either is more keenly aware of sounds or more interested in their meaning that the term child. Prematures are highly distracted by footfalls or voices in the corridor, by traffic noises, and by the sound of other babies crying…Older preemies often manifest the ‘hark’ response — suddenly stopping in their play and whispering in a startled voice ‘What’s that?’ at the hiss of a radiator, a cricket chirp, or a fire siren blocks away. On the visual sensory side the premature babies were more fascinated and distracted by a yellow pencil than by any of the mental test objects…”

“Lingual-motor control: …difficulties in achieving correct pronunciation…may persist in baby talk…The difficulties of the little Dionne girls in learning to talk intelligible French are probably only slightly greater than those of many prematurely-born children.”

Manual motor control:

“[delays in] use of index finger for pointing and for pincer grasp. Prehension is often carried out with all four digits opposing the thumb, rather than merely with thumb and index finger, which is more commonly used by fullterm babies…Often after prolonged effort to reach they exhibit tremor. Their play with toys is executed with choppy, slap-dash movements. They over-reach, spill, scatter; [and]…have a passion for throwing toys to the floor or brushing them aside with petulant gestures…Sometimes prematures work at such a task exerting the utmost effort to make the precise coordinations, until their reserve of patience and nervous control is at an end and they ‘go all to pieces.’ “

Postural and locomotor control:

“This develops later in premature than in term children and once the premature achieves ambulation, he is usually less graceful and less smoothly flowing in his motor responses than the term child. Our older prematures are more often described as awkward, clumsy, as having a lunging gait or as having poor posture than our term children.”

Activity:

“In amount of activity premature children seem to go to two extremes. On the one hand [they] are tense, jumpy, hyperactive little creatures that seem to be mounted on springs; and on the other [they] are floppy, soggy, lazy babies and sluggish, clumsy children, slow and deliberate in their motions.”

Emotionality:

“…irascible, petulant, and more often shy and negativistic than the term child. Prematures are upset by slighter stimuli; they are capable of standing just so much, then they explode in a tantrum or a panic.”

Attention:

“The attention span of the premature is very short; he flits from toy to toy in the playroom; and at the test situation he is extremely susceptible to distraction. It is often difficult to get him to stick to a difficult task and to see it through, particularly if it is possible for him to appeal for adult help in finishing it. Conversely — and this seems a contradiction — the premature sometimes works to the point of nervous exhaustion on a difficult motor task. He continues working at a high level of interest and coordination until he collapses in rage from fatigue and frustration.”

Other observations:

“Questions asked during a 30-minute period in the playroom was consistently higher for premature boys than for controls”… “[many] prematures were predominantly left-handed” …”Premature boys displayed more temper than girls, whereas the girls displayed more stubbornness, passive resistance, and negativism. Prematures were also more fearful of persons and animals than their [term] siblings, but the siblings showed more fear reactions of other types.”

“Much of the behavior of prematures is understandable if we assume that he is more sensory than motor. There is good evidence that his sensory development is in advance of his motor control, age for age. The premature is highly receptive to stimulation, particularly to auditory stimulation; but he is less capable than the term child of making an adequate motor adjustment to the stimulus…The frustration that comes from inability to manipulate materials may well become a source of irascibility that is expressed in petulancy and in the tendency to throw or scatter toys. Such a condition might well lead to habits of inattention, flitting interest in toys and subsequently to versatility of interests and development of many hobbies — a trait that seems to characterize adult prematures. The prematures’ stubborn refusals, withdrawals from proffered toys, and their tendency to give up on a task before its completion may be a way of reducing the amount of stimulation they receive. Superior sensory ability…might also lead to certain types of aesthetic appreciation that seem to crop out often among prematures. Indeed, the word ‘sensitive’ as used by the layman begins to take on a literal meaning when applied to the premature.”

Part 2

Here are some more excerpts from “A Behavior Syndrome Characterizing the Prematurely-Born Child” by Mary Shirley (a doctor at Harvard) published in Child Development. Vol. 10, no. 2, June 1939:

“In auditory sensitivity, the premature child either is more keenly aware of sounds or more interested in their meaning than the term child.  Prematures are highly distracted by footfalls or voices in the corridor, by traffic noises, and by the sound of other babies crying … Older premature children often manifest the ‘hark’ response, –suddenly stopping in their play and whispering in a startled voice ‘What’s that?’ at the hiss of a radiator, a cricket chirp, or a fire siren blocks away…prematures have difficulty achieving correct pronunciation.  They persist longer in baby-talk…The difficulties of the little Dionne girls [the Dionne quintuplets] in learning to talk intelligible French probably are only slightly greater than those of many prematurely-born children….Prehension often is carried out with all four digits opposing the thumb rather than merely with thumb and index finger…often after prolonged efforts at reaching they exhibit tremor.  Their play is executed with choppy, slap-dash movements.  They over-reach, spill, scatter; and prematures of 12 and 18 months have a passion for throwing toys to the floor or brushing them aside with petulant gestures…Sometimes prematures work at such a task [as filling in a pegboard] exerting the utmost effort to make precise coordinations, until their reserve of patience and nervous control is at an end and they ‘go all to pieces’…Once the premature achieves ambulation, he usually is less graceful and less smoothly-flowing in his motor response than the term child.  Our older prematures are often described as awkward, clumsy, as having a lunging gait, or as having poor posture than our term children…In amount of activity, premature children seem to go to two extremes.  On the one hand they are tense, jumpy, hyperactive little creatures that seem to be mounted on springs; on the other… they are sluggish and clumsy children, slow and deliberate in their efforts…Achievement of bowel and bladder control is slower and more difficult … Emotionally the premature child is more irascible, petulant, and more often shy and negativistic than the term child.  Prematures are upset by slighter stimuli; they are capable of standing just so much, then they explode in a tantrum or a panic … The attention span of the premature is very short; he flits from toy to toy in the playroom; and..is extremely susceptible to distractions.  It is often difficult to get him to stick to a difficult task and to see it through … Conversely — and this seems a contradiction — the premature sometimes works to the point of nervous exhaustion until he collapses in a rage from fatigue and frustration…. The median number of questions asked during a 30 minute period was consistently higher for premature boys than for controls…”

This was all written 60 years ago!

Source

http://www.prematurity.org/research/helen-1939.html

Premature Infants – 42 Developmental Risks

Prematurity Research Disproves the Theory that Preemies Catch Up By Age Three

This infant was born at 24.5 weeks. He spent three months in the neonatal intensive care unit.


By Patti Wrape

I am the mother of natural twin boys (my first children) who were born without any prior warning or complications at 27.5 weeks gestation.In the course of advocating for my premature twin sons (see my goals for advocating for children born premature), I conducted online research into developmental delays in preemies.  There seems to be a medical myth that preemies “catch up” developmentally.   In fact, recent research seems to suggest that they often do not, at least not without intervention. Researchers at Yale University have conducted brain scans that show key areas of preemies brains appear to be less developed than non-preemies.  The earlier the preemie, the less developed these key brain areas appeared to be.  Another researcher described a sleeper phenomenon in which preemies appeared developmentally okay until about age three.  From my own experience and discussion with other preemie parents it seems that preemies may exhibit knowledge or developmental spikes and may exhibit traits characteristic of autism.

All parents of preemies need to be informed of developmental risks, should have their children undergo frequent developmental screenings (including from age 3 and up) and should seek early intervention as appropriate.”

Please Note: Most source documents listed below can be retrieved from the National Library of Medicine, PubMed Online Database. www.ncbi.nlm.nih.gov/

1. Children born about 3 months prematurely are 3 to 4 times more likely to struggle in school than children born full term. Compared with children born full term, students born prematurely were more likely to repeat a grade of school (33% versus 18%), receive special education (20% versus 5%) and require extra help with reading, spelling, math, handwriting, speech/language and occupational or physical therapy (16% versus 6%). Study conducted at University of Buffalo, reported in Paediatric & Perinatal Epidemiology, October 2000.
2. Some studies have estimated that as many as 40 to 50% of children born prematurely will have some sort of learning disability. A study was conducted in which none of the premature children suffered from major “preemie” related health problems such as cerebral palsy, chromosonal abnormalities, hearing loss or mental retardation. According to one of the authors of the study: “In a sense, the children in our study represented a kind of sleeper phenomenon”, none had noticeable disabilities. There’s no way to pick up on some of these developmental problems in the first two years of life, so many of these children showed no outward signs of disabilities.” Predicting the Future of Premature Babies, Testing Previews Future Learning Problems, By Holly Wagner

3. Almost half of children who survive extremely preterm birth have neurologic and developmental disabilities. Disability Risk for Extremely Premature Babies, Source: Yale University, (http://www.yale.edu/) Posted 10/18/2000.

4. Brain scans of children born prematurely show key areas of the brain are much smaller than those of children born at full term. The study conducted by Yale researchers is the first to relate brain abnormalities in preemies to cognitive outcome and perinatal risk factors. The differences in brain volume on average were dramatic in all regions with reductions ranging from 11 to 35%. While not all preemies showed brain abnormalities, those born at a younger gestational age were most affected. The magnitudes of the abnormalities were directly proportional to how early the children were born and were strongly associated with the IQ of the children at age 8 years. “Premature birth at less than 1,000 grams birth weight (approximately 2 lbs) is a major cause of developmental disability. Infants in this birth weight range represent almost 1% of all births in our country, and the survival rate of these infants is well over 80%, but the incidence of handicap is high. By age 8 years, over 5% are in special education or receiving extensive resource room help. One fifth have already repeated a grade of school.” according to Dr. Laura Ment. “The study shows that when brains develop prematurely outside of the womb, they are vulnerable to developmental disturbances.” Dr. Bradley Peterson. Brain Size in Premature Infants Significantly Smaller than Full Term Babies; Source: Journal of American Medical Association 10/18/2000

5. A quarter of a million babies a year are born prematurely in the United States and the ones doctors can save are getting smaller and smaller. But not getting the chance to finish their time in the womb may come back to haunt these children. A study conducted by British researchers showed that 52% of preemies had problems at age 2 ½, though many other prematurity related problems did not show up until age 5. University of Nottingham, published in New England Journal of Medicine, source EXN Staff, October 17, 2000.

6. Children born extremely prematurely, weighing 2 lbs or less at birth, experience significant learning disabilities that persist into their teenage years. A study conducted at McMaster University in Hamilton, Ontario, Canada, followed 150 premature babies into their teens. Nearly half were receiving special education assistance, compared with just 10% of a control group of children who were not born prematurely but were similar in gender, age and social class. 25% of “preemies” had repeated a grade, compared with just 6% of the control group. Fewer than half of the smallest preemies (those born weighing 1 lb, 9 oz and under) scored in the normal range on most intelligence and achievement tests. Preemies Have Trouble Into Adolescence, Chicago AP

7. The outlook for children born extremely prematurely is precarious at best. Many parents do not know what to expect and their doctors do not know what to tell them. A new study from the United Kingdom suggests that extremely preterm babies who survive to leave the hospital have about a 50-50 chance of being free of disability at age 2 ½ years. Extremely Premature Babies at Risk of Severe Disability, New England Journal of Medicine 2000; 43. 378-384, 429-430.

8. Currently 1 in 10 babies in the United States is born prematurely. Half of extremely premature infants who survive have mental or physical disabilities, a quarter of them severe. Boys are more likely than girls to have problems. Premature Babies: Half of Them Have Disabilities, New England Journal of Medicine 2000; Aug 10; 343 (6): 378-84.

9. It has been more than 20 years since doctors began saving extremely premature infants and about a decade since advances in neonatology vastly improved the survival of babies with very low birth weight – those weighing less than 1,500 grams, or 3 lbs, 4 oz. The tiniest of these babies, micropreemies as they are called, are born as much as 14 weeks early and weigh less than 750 grams, or 1 lb., 1 oz. For the first time thousands of such children are now well into their school years. Conventional medical wisdom, based on previous studies, had been that premature children who were not seriously physically disabled, would catch up to other youngsters by age 5. Many do just fine, but as the first large group of tiny babies grows up, new research is showing that academic and behavioral problems often surface in the school years. As Premature Babies Grow, So Can Their Problems, Sheryl Gay Stolberg

10. A study was done in Israel that measured the emotional and behavioral development of prematurely born children. It found that premature children had higher levels of anxiety, depression and aggression than full term children, and that they had a lower self concept. Premature children were found to have more disturbances at home and school. The smaller the birth weight, the less emotionally adjusted the child will be. Rachel Levy Shifft and Gili Einat, Journal of Clinical Child Psychology V 23 p 328-9

11. Extremely low birth weight infants are at significant risk of neurologic abnormalities, developmental delays and functional delays at 18 to 22 months corrected age. Neurodevelopmental and Functional Outcomes of Extremely Low Birth Weight Infants in the National Institute of Child Health and Human Development Neonatal Research Network 1993-1994. Betty R. Vohr, Linda L. Wright, Anna M Dusick, Lisa Mele, Joel Verter, Jean J. Steichen, Neal P. Simon, Dee C. Wilson, Sue Brolyes, Charles R. Bauer, Virginia Delaney-Black, Kimberely A. Yolton, Barry E. Fleisher, Lu-Ann Papile, Michael D. Kaplan. Pediatrics Vol 105, No 6, June 2000, p 1216-1226.

12. Changing patterns of neurologic and developmental functioning between 1 to 7 years of age were studied in very low birth weight infants. Children received a neurologic assessment at 1 year and were reexamined at age 7. The age 1 and age 7 neurologic assessments were significantly related. The findings of the study indicate that a neurologic classification at 1 year of age provides a guide for monitoring very low birth weight infants and can be helpful in alerting school personal to potential needs. Neurodevelopmental and School Performance of Very Low Birth Weight Infants: A Seven Year Longitudinal Study, BR Vohr and CT Garcia Coll, American Academy of Pediatrics, Volume 70, Issue 3, pp 345-350. 9/1/1985.

13. Comparisons were made among 4 birth weight groups to examine the effect of birth weight on the classroom behavior of children entering elementary school. Extremely low birth weight children had lower attention and language skills, overall social competence, scholastic competence and athletic ability than all other birth weight groups as measured by classroom teachers, even when controlling for neonatal stay, child’s gender and ethnicity, and maternal education. All low birth weight children had lower attention and language skills and scholastic competence and higher daydreaming and hyperactivity scores then normal birth weight children. The classroom behavior of low birth weight children was rated by teachers as poor, even for children who had not failed a grade. Low birth weight children who are on grade level may still be at risk for problems. Classroom Behavior of Very Low Birth Weight Elementary School Children, Klebanov PK, Brooks-Gunn J, McCormick MC, Columbia University Teachers College, New York, NY, Pediatrics 1994, Volume 94, Issue 5, pages 700-708. 11/01/1994.

Educational Status and School Related Abilities of Very Low Birth Weight Premature Children, Ross G, Lipper EG, Auld PA, Department of Pediatrics, Cornell University Medical College, New York, NY, Pediatrics December 1991, 88 (6): 1125-34.

14. Eighty Eight premature children with birth weights less than or equal to 1,500 grams were evaluated at ages between 7 to 8 years old to determine their academic status in comparison with those of a matched full term group. Results showed that a much higher proportion of the premature children required special education interventions (48%) than either the full term (control group) children (15%), or the New York State elementary school population (10%). More than half of the premature children who received educational intervention were neurologically impaired or had below normal intelligence. The entire group of premature children differed significantly from the matched full term group on IQ score and on tests of verbal ability, school achievement and auditory memory. Six Year Neurodevleopmental Follow Up of Very Low Birthweight Children, Litt R, Joesph A, Gale R Department of Neonatalogy, Bikur Holim Hospital, Israel, Israel Journal of Medical Science, May 1995. 31 (5) 303-8

15. Twenty Four children born preterm in 1985 with very low birthweights were followed until the age of 6. The mean verbal IQ of these children was significantly lower than the control group. Four of the children had major disabilities and minor neurological deficit was found in another 7. These findings point to possible future learning disabilities and point out the importance of long term follow up in order to identify and address these specific educational needs. Risk Factors for Major Neurodevelopmental Impairments and Need for Special Education Resources in Extremely Premature Infants. Msall ME, Buck GM, Rogers BT, Merke D, Catanzaro NL, Zorn WA. Journal of Pediatrics, October 1991, 119 (4) 606-14.

16. A study comprised of 100 infants born between 24 to 28 weeks gestational age from 1983 to 1984, indicated that 25% of the children had major impairments, such as cerebral palsy, blindness and mental retardation. Another 9% required special education resources and 48% of the additional children would possibly need special education resources. Intellectual and Functional Status at School Entry of Children who Weighed 1,000 Grams or Less at Birth: A Regional Perspective of Births in the 1980’s. Saigal S, Szatmaria P, Rosenbaum P, Campbell D, King S. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada, Journal of Pediatrics, March 1990. 116 (3) 409-16.

17. A study was conducted on 90 children (average age at time of study 5 ½ years) who were born between 1980 to 1982 and weighing between 501 to 1,000 grams at birth. Of the children, 43% were shown to be at mild to high risk for future learning disabilities. Very Low Birthweight Boys at the Age of 19. Ericson A, Kallen B, Centre for Epidemiology, National Board of Health, Stockholm, Sweden, Arch Dis Child Fetal Neonat Ed, May 1998, 78 (3) 171-4.

18. Long term follow-up (to 18-19 years of age) was made of 260 singleton boys whose birthweight was less than 1,500 grams. These boys had more visual and hearing impairments and were at much higher risk of cerebral palsy and other signs of mental impairment, evident as lower intelligence test scores and shorter schooling. School Performance at 9 Years of Age in Very Premature and Very Low Birth Weight Infants: Perinatal Risk Factors and Predictors at Five Years of Age.

19. A study conducted by the Institute of Preventive Health Care in the Netherlands found that at the age of 9, 19% of very premature children were in special education. Of the children in mainstream education, 32% were in a grade below the appropriate level for age and 38% had special assistance. Collaborative Project on Preterm and Small for Gestational Age Infants in the Netherlands, Hille ET, Den Ouden Al, Bauer L, Van Den Oudenrijn C, Brand R, Verloove-Vanhorick SP. TON Institute of Preventative Health Care, Leiden, The Netherlands, Journal of Pediatrics, September 1994, 125 (3) 426-34.

20. Two Hundred and eighty nine very low birthweight children born in New Zealand in 1986 were assessed at 7 to 8 years of age on measures of behavior, cognitive ability, school performance and the need for special education. The outcomes were compared with a sample group of over 1,000 children. The result was that the very low birthweight children had significantly higher rates of problems and poorer rates of functioning across all outcome measures than the general child sample. These differences persisted even after control for variability in social, family and other characteristics of the two samples and for the degree of sensineural disability. These findings are consistent with a growing body of research evidence which suggests that premature and very low birth weight infants are at increased risk of functional impairment in middle childhood. Cognitive, Educational and Behavioral Outcomes at 7 to 8 Years in a National Very Low BirthWeight Cohort. Horwood LJ, Mogridge N, Darlow BA, Christchurch Health and Development Study, Christchurch School of Medicine, New Zealand. Arch Dis Child Fetal Neonatal Ed, July 1998, 79 (1) F 12-20.

21. A study was conducted of 243 prematurely born very low birthweight (less than 1501 grams) children with a normal birthweight, full term control group for comparison. The children were evaluated at 7 to 8 years of age and findings indicate that the children born preterm (both male and female) were rated by their teachers as expressing more behavior problems than their controls and were less well adjusted to the school environment. The deficits noted in the preterm children applied across social class. It is speculated that the problem behaviors reflect a failure in self regulatory functions.
Behavioral Adjustment in School of Very Low BirthWeight Children, Sykes DH, Hoy EA, Bill JM, McClure BG, Halliday HL, Reid MM. School of Psychology, Queen’s University, Belfast, Northern Ireland, Journal of Child Psychology, Psychiatry, March 1997, 38 (3) 315-25.

22. A study was conducted which categorized children into 4 birthweights grom extremely low to normal and then compared them on indicators of school achievement including: grade failure, placement in special classes, classification as handicapped and math and reading achievement scores. Results indicated that as birthweight decreased, the prevalence of grade failure, placement in special classes and classification as handicapped increased, even when controlling for maternal education and neonatal stay. Extremely low birthweight children scored lower than all other birthweight groups on math and reading achievement tests. School Achievement and Failure in Very Low Birth Weight Children. Klebanov PK, Brooks-Gunn J, McCormick MC. Colombia University, Teachers College, New York. Journal of Dev. Pediatrics, August 1994, 15 (4) 248-56.

23. A study examined achievement, behavior and neuropsychological outcomes at early school age in a population of children born at less than 750 grams, and compared them to a full term birth control group. The preemie children performed more poorly than higher birth weight children on tests of math, in language, perceptual motor and attentional skills. Findings document specific weakness in achievement and neuropsychological skills in children less than 750 grams at birth weight and support the need for early identification and special education interventions. Achievement in Children with Birthweights less than 750 Grams with Normal Cognitive Abilities. Taylor HG, Hack M, Klein N, Schatschneider C. Dept of Pediatrics, Case Western Reserve University School of Medicine, Journal of Pediatric Psychology, Dec 1995, 20 (6) 703-19.

24. Eight hundred and seventy three children in an entire school grade in a Swedish community were studied to show the effect of birth weight. Low birth weight children had lower school performance and IQ scores at age 13 than normal birth weight children irrespective of parental socio-economic status. School Performance and IQ Test Scores at Age 13 As Related to Birth Weight and Gestational Age. Lagerstrom M, Bremme K, Eneroth P, Magnusson D. Dept of Psychology, Stockholm, Sweden. Scandanavian Journal of Psychology 1991, 32 (4) 316-24.

25. A study compared 65, 9 year old children born in 1976 who were very low birthweight and were free of neorological impairment with 65 “normal”, full term, children who were comparitive in background, etc. to the low birthweight group. Very low birth weight children scored significantly lower than controls on the WISC-R, Bender-Gestalt, Purdue Pegboard, subtests from the Woodcock Johnson Cognitive Abilities Battery and reading and mathematics achievement tests. Children Who Were Very Low Birthweight: Development and Academic Achievement at 9 Years of Age. Klein NK, Hack M, Breslau N. College of Education, Cleveland State University, Journal of Developmental Behavior Pediatrics, Feb 1989, 10 (1) 32-7.

26. A nine year follow up of 116 children born in 1971 to 1974 with a birthweight of 1,500 grams or less found that 59 had died and 7 had extreme handicaps or blindness. The low birthweight children without extreme handicaps were found to have impaired motor function, speech defects and impaired school achievements more often than the controls. Nine Year Follow Up of Infants Weighing 1,500 grams or Less at Birth. Michelsson K, Lindahl E, Parre M, Helenius M. Acta Paediatr Scand. November 1984; 73 (6): 835-41.

27. Thirty five of 45 long term survivors with birth weights of 1,000 grams or less whor were cared for in the University of Washington, Seattle, Neonatal Intensive Care Unit, from 1960 to 1972 were examined at an average age of 10 ½ years. Twenty eight percent had one or more major neurological or sensory handicap, 64% have been or are presently in a special education program. Only 28% are currently rated by their teachers to be achieving at or above grade level. Arithmetic reasoning, mathematics achievement and reading comprehension were specific weaknesses. Fine and gross motor skills were impaired. Perceptual skills were impaired to a lesser degree. School Performance of Children with Birth Weights of 1,000 Grams or Less. Nickel RE, Bennett FC, Lamson FN. Am J Dis Child, Feb 1982; 136 (2): 105-10.

28. This study examined the relationship between very low birthweight children and possible developmental delay in the absence of frank developmental disability. Subjects were asymptomatic for disabling conditions but apparently well, very low birthweight, children were consistently at greater risk for both moderate and severe measures of delay across four functional areas. Relation Between Very Low Birth Weight and Developmental Delay Among Preschool Children Without Disabilities. Schendel DE, Stockbauer JW, Hoffman HJ, Herman AA, Berg CJ, Schramm WF. Developmental Disabilites Branch, Centers for Disease Control and Prevention, Chamblee GA, Usaam J. Epidemiol, November 1, 1997; 146 (9): 740-9.

29. At the adjusted age of 5 years the development of 106 children born 5 or more weeks before term was compared with the development of 103 children born at term. No children with cerebral palsy were included and the groups were matched in terms of sex, age, birthplace, race and residential location. The results indicated a significant difference between the two groups including preterm children having small involuntary hand movements, less competent gross motor ability, poorer verbal performance and more variability in behavior postural response and balance. A higher than average incidence of minor motor, speech, behavior and learning problems in early school years is probable. Language and Motor Development in Pre Term Children: Some Questions. Le Normand MT, Vaivre-Douret L, Delfosse MJ. INSERM, Hospital de La Salpetriere, Paris, France. Child Care Health Dev, March 1995; 21 92) 119-33.

30. A study conducted in a Southern Swedish population compared extremely preterm children to a control group of full term children at age 10. Health, cognitive development, school achievement and behavior were evaluated. Thirty eight percent of the extremely preterm children performed below grade level at school. Thirty two percent had general behavioral problems and 20% had attention deficit hyperactivity disorder compared with 10% and 8 % respectively in the full term group. The study concluded that extremely preterm children require intervention to support development and reduce behavioral problems. Ten Year Follow Up of Children Born Before 29 Gestational Weeks: Health, Cognitive Development, Behaviour and School Achievement. Stjernqvist K, Svenningsen NW. Department of Psychology, Lund University, Sweden. Acta Paediatr, May 1999; 88 (5): 557-62.

31. Cognition, school performance and behavior were assessed at 8 years of age in 132 very low birth weight children who were otherwise free of major sensineural impairments and were compared with a control group of full term normal birthweight children. While the very low birth weight children were developing normally in many academic and social areas they were significantly inferior on tests of cognition, including tests of intelligence and visual memory and on teachers’ reports of motor skills and intelligence. Proportionally more very low birth weight children (20.5%) than normal birth weight children (5.9%) were reported by their parents to be not coping at school. Cognition, School Performance and Behavior in Very Low Birth Weight and Normal Birth Weight Children at 8 Years of Age: A Longitudinal Study. Rickards AL, Kitchen WH, Doyle LW, Ford GW, Kelly EA, Callanan C. Division of Pediatrics, Royal Women’s Hospital, Melbourne, Australia. J Dev Pediatr, December 1993; 14 (6): 363-8.

32. The intellectual, psychoeducational and functional status of a group of 129 extremely low birth weight children born between 1977-1981 and weighing 501 to 1,800 grams at birth were compared with a matched control group. The children were tested at an average unadjusted age of 8 years. The average IQ was 91 for extremely low birth weight children and 104 for the control group. Between 8 to 12% scored in the abnormal IQ range compared with 1 to 2% of the control group. The low birth weight children did less well on reading, spelling and math tests and their motor performance and visual motor integration were poorer. Approximately 15% of the extremely low birth weight study participants perfomred in the abnormal range on the Vineland Adaptive Behavior Scales. Although about 2/3rds fo the low birth weight children performed in the normal range on intellectual measures they were significantly disadvantaged on every measure tested. Cognitive Abilities and School Performance of Extremely Low Birth Weight Children and Matched Term Control Children at Age 8 Years: A Regional Study. Saigal S, Szatmari P, Rosenbaum P, Campbell D, King S. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. J Pediatri, May 1991; 118 (5): 751-60.

33. A study was conducted to examine developmental and educational outcomes in a group fo predominantly white, middle class, extremely low birth weight children (less than 1,000 grams birthweight). Fifty four extremely low birthweight children with an average age of 7 were compared to a children in a control group matched for gender, race and socioeconomic factors and were sorted to low and normal birthweight groups. Teachers’ reports, special education evaluations, and test of cognitive, motor, language and visual motor integration abilities were studied. Fifty percent of the extremely low birth weight children were in regular classrooms compared to 70% of low birth weight children and 93% of full term children. The extremely low birth weight children scored significantly lower than the comparison groups on all tests. While 79% of the extremely low birthweight children had average cognition scores, they average 14 to 17 points lower than the two comparison groups. Twenty percent of the extremely low birth weight children had significant disabilities including cerebral palsy, mental retardation, autism and low intelligence with severe learning problems. The study concluded that there is an increasing need for special services with decreasing birth weights. Even with optimal socioeconomic environments, 20% of extremely low birthweight children are significantly disabled and 1 out of every 2 extremely low birth weight children requires special educational services. Extremely Low Birth Weight Children and Their Peers, A Comparision of School-Age Outcomes, Halsey CL, Collin MF, Anderson CL. Loyola University Medical Center, Maywood, ILL, USA Arch Pediatric Adolesc Med August 1996; 150 (8): 790-4.

34. Children with a birthweight of 2,000 grams or less born in Merseyside, England from 1980-1981 were assessed at age 8. The children and a matched control group were assessed using the Wechsler Intelligence Scale for Children (WISC) , the Neale analysis of Reading ability and the Stott-Moyes-Henderson test of Motor Impairment (TOMI). Children with low birth weight had a lower WISC IQ score, a lower reading age, and poorer motor performance. Clinical and Subclinical Deficits at 8 Years in a Geographically Defined Cohort of Low Birthweight Infants. Pharoah PO, Stevenson CJ, Cooke RW, Stevenson RC. Department of Public Health, University of Liverpool, Arch Dis Child, April 1994; 70 (4): 246-70.

35. Fifty one children who were born at the same hospital in Liverpool, England, with weights of 1,250 grams or less were followed through age 8. The extremely low birth weight group of 8 year olds were compared with a control group of the same age, race, economic group and sex. The low birth weight children performed less well on basic math tests, spelling tests, and tests of motor impairment. Twenty three percent of very low birth weight children were having difficulty with one or more school subjects compared with 19% of controls and 26% had difficulties in 2 or more areas compared with 3% of the control group. Teachers identified characteristics typical of emotional disorders and overactivity more frequently among the very low birthweight group. The study concluded that children with birthweights of 1,250 grams or less and no major impairment have a high frequency of learning difficulties that become more apparent with advancing age. Outcome at 8 Years for Children with Birth Weights of 1,250 Grams or Less. Marlow N, Roberts L, Cooke R. Department of Child Health, Liverpool Maternity Hospital. Arch Dis Child, March 1993; 68 (3 Spec No): 286-90.

36. Neurodevelopmental, health and growth outcomes for 28 six year olds weight birthweights of less than 1,001 grams were compared with a control group of 26 full term birth children. Sixty one percent of the extremely low birth weight children had mild or moderate to severe neurological problems compared with the control group children (23%). A significant portion of extremely low birthweight children had no severe disabilities, but many had dysfunctions likely to affect learning and behavior in school. Neurodevelopmental, Health and Growth Status at Age 6 Years of Children with Birth Weights Less than 1,001 Grams. Teplin SW, Burchinal M, Johnson-Martin N, Humphry RA, Kraybill EN. Clinical Center for the Study of Development and Learning, Frank Porter Graham Child Development Center, University of North Carolina, J Pediatri, May 1991; 118 (5): 768-77.

27. Thirty four long term survivors of a five year period (1977-1981) weighing 1,000 grams or less at birth were followed up at 8 to 11 years of age. Three (8.8%) of the children had severe functional handicap, seven (20.6%) had moderate impairments with the need for special schooling. Twenty four (70.6%) attended normal school but 7 (20.6%) needed special help. Infants Weighing 1,000 Grams or Less at Birth. Outcome at 8-11 Years of Age. Vekerdy-Lakatos Z, Lakatos L, Ittzes-Nagy-B. Department of Pediatrics, University Medical School, Debrecen, Hungary, Acta Paediatr Scand Suppl 1989; 360: 62-71.

38. This study tested the hypothesis that very low birth weight children (less than 1.5 kg) whose head size is not normal by 8 months (adjusted age) have significantly poorer growth and neurocognitive abilities at school age than very low birth weight children with a normal head size at eight months. A group of 249 children born from 1977 to 1979 were evaluated at age 8 to 9 years; the 33 children with subnormal head sizes at the age of 8 months had significantly lower average birth weights and higher neonatal risk scores (71 versus 53) and at the age of eight years had a higher incidence of neurologic impairment (21% versus 8%) and lower IQ scores (average verbal 84 versus 98%). The conclusions of the study indicate that in very low birth weight infants, pernatal growth failure, as evidenced by a subnormal head circumference at 8 months of age, is associated with poor cognitive function, academic achievement and behavior at 8 years of age. Effect of Very Low Birth Weight and Subnormal Head Size on Cognitive Abilities at School Age. Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E. Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH. New England Journal of Medicine, July 25, 1991; 325 (4): 231-7.

39. In 1990 to 1992 a study was conducted in which randomly selected and evaluated low birthweight and normal birthweight children from the 1983-1985 newborn lists of two major hospitals in Southeast Michigan. Low birth weight children scored significantly lower than normal birth weight children on tests measuring language, spatial., fine motor, tactile and attention abilities with appropriate controls for site, race, maternal IQ and education. Analysis revealed that test performance varied within birth weight levels and that performance continued to improve with increased birth weight well above 3,000 grams. Low Birth Weight and Neurocognitive Stauts at Six Years of Age. Breslau N, Chilcoat H, DelDotto J, Andreski P, Brown G. Department of Psychiatry, Henry Ford Health Sciences Center, Detroit, MI. Biol Psychiatry, Sept 1, 1996; 40 (5): 389-97.

40. Survival of extremely low birth weight infants, (less than 1,000 grams) has increased. From the period of 1943 to 1945 the survival rate of infants born weighing less than 800 grams was 0% but increased to 49% to 70% for the period 1994-1995. Rates of cerebral palsy. mental retardation, blindness and deafness have remained stable in the 1980’s and 1990’s. There is evidence. however, that the percent of functional limitations may be increasing as the requirement for special education resources among very low birthweight infants remains high at 44% to 56%. Neuropsychological and Functional Outcomes of Very Low Birth Weight Infants, Vohr BR, Msall ME. Women and Infants Hospital, Child Development Center of Rhode Island Hospital, Brown University School of Medicine, Providence, RI. Semin Perinatol, June 1997; 21 (3): 202-20.

41. A study was conducted in which very low birth weight infants were compared with heavier low birth weight infants and normal birth weight children to assess the risk of behavior problems and school difficulty. Analysis revealed that 34% of very low birth weight children could be characterized as having school difficulty compared with 20% of heavier low birth weight children and 14% of normal birthweight children. Very low birthweight and hyperactivity scores contributed, independent or other sociodemographic factors, to the risk of academic problems. Very Low Birth Weight Children: Behavior Problems and School Difficulty in a National Sample. McCormick MC, Gortmaker SL, Sobol AM. Department of Behavioral Sciences, Harvard School of Public Health, Boston, Mass. J Pediatr, Nov 1990; 117 (5): 687-93.

42. A review of 20 years experience with neonatal intensive care for very low birth weight infants indicates that an increasing proportion survive free of moderate to severe handicap. However, increasing literature suggests that early findings may be insufficient to characterize later outcomes, particularly problems encountered as children enter school. The study concludes that further definition of long term outcomes for very low birth weight children is critical to assess the utility of neonatal intensive care unit interventions and at the individual level for counseling families as to the health and educational needs of these children. Long Term Follow Up of Infants Discharged from Neonatal Intensive Care Units. McCormick MC. Joint Program in Neonatology, Harvard Medical School, Boston, Mass. JAMA, March 24-31, 1989; 261 (12): 1767-72.


The toddler in this picture was taken at four years of age. This is the same child as the premature infant in the photo at the start of this article. Many of the items in this article have been and are being experienced by this toddler.

Source:

http://www.prematurity.org/research/not-catchingup3.html

Please note photos have been added by the poster and not the author of the article.

Prematurity Factors Or Abuse And Neglect Indicators

Research on Prematurity Impacts

Research studies that all of us should have on hand to show the school, the pediatrician, and any other institution or person who deals with our premature children.

Source:

http://www.prematurity.org/research/helen-packets-comments.html

By Helen Harrison

See Also: Helen Harrison’s Bibliography of the Long Term Effects of Prematurity

Functional Assessment of a Multicenter Very Low-Birth Weight Cohort at Age 5 Years

Palta, Sadek-Badai, Evans et al. Archives of Pediatric and Adolescent Medicine, 2000;154:23-30.

“This is a multi-center study out of U of  Wisconsin at Madison and U of Iowa (Iowa City).  The participants are more than 400, predominantly Caucasian, very low birth weight preemies (under 1500 grams) born in the late 1980s and early 1990s. The average gestational age is 29 weeks.

This study looks at differences in functional outcomes (mobility, self-care, social) among preemie children who survived before and after the widespread use of steroids and surfactant.

Because the teen studies I am also sending you come from the pre-surfactant era of NICU care, there is always the question of whether or not such studies are still relevant. Most people assume that outcomes have improved in the more recent era, but this large and recent study shows that the CP rate hasn’t changed pre- or post-surfactant/steroids (13%), and that functional outcomes such as mobility and social skills appear to have worsened.

Although there is a current 13% CP rate, 30% of VLBW preemies now have seriously subnormal “mobility” — that is, they score more than 2 standard deviations below the norm on tests of physical functioning.  This is the physical equivalent of retardation — having an IQ below 70. 51% of VLBW preemies have scores 1 standard deviation below the norm (the physical equivalent of an IQ of 84 or below). That so large a percentage of physically compromised preemies don’t have a diagnosis should be of concern (IMHO).

32% of the VLBW children were one standard deviation below the norm in self-care skills, and 39% had subnormal social skills.”

Developmental Coordination Disorder in Extremely Low Birthweight Children( =/<800 grams) at 8.9 Years.”

Holsti, Grunau, and Whitfield. Pediatric Research, 1999;45:245A, #1443. (The full study has not been published yet to my knowledge.)

“In this study, out of U of British Columbia, Vancouver,  impaired physical functioning that wasn’t considered to be cerebral palsy, was referred to as “Developmental Coordination Disorder (DCD).” The 114 children in the study were born between 1982 and 1987.  40 (35%) of the children had either CP and/or subnormal IQ (below 85) and/or sensorineural problems and were *excluded* from the study.  Of the remaining 74 “normal”children, 51% were classified as having DCD.  DCD was defined as being one standard deviation below the norm in tests of fine and large motor skills.”

Prediction of Written Output Ability in Extremely Low Birth Weight (ELBW; =/<800g) Children from Age 4 to 8 Years.”

Grunau, Whitfield, McConnell et al. Pediatric Research 1999;45:245A, #1440. (The full study has not been published yet to my knowledge)

Also from Vancouver and involving the same children described above, this study reports that difficulties with written work are 8 times more common among “normal” preemies than among fullterm controls.  These problems (at age eight) were predicted by low scores at age 4 1/2 in numerical problem solving, pencil copying, and visual perception.  This study was presented at last year’s Society for Pediatric Research meeting in San Francisco.  Sample essays by the preemies and the fullterm children were displayed.  The differences in handwriting, continuity of thought, expression, etc., were striking.

The authors state: “This study highlights continuities in visual-motor perceptual functioning and learning problems….Story writing is a complex activity requiring multifaceted problem-solving in addition to pencil skills.”

Emotional and Behavioral Adjustments of’ Normal’ Very Low Birth Weight Children Compared to Controls at 7 Years of Age.”

Kamaya, Moddemann, and Casiro. Pediatric Research. 1996;39:269A #1597. (Not yet published to my knowledge.)

This study, from University of Manitoba in Winnipeg, looked at 48 “non-handicapped” very low birthweight preemies and found they had intellectual, academic, visual-spatial and attentional weaknesses compared to term controls.  Behavior and social competence of these children was rated lower by parents and teachers with significant differences found in somatic complaints, anxiety/depression, social problems, attention problems, and aggressive behavior.

21% of the preemies had scores in the abnormal clinical range on Total Behavior Problems; 19% were in the abnormal range on somatic complaints; 17% were in the abnormal clinical range on attention; 15% were in the abnormal clinical range on “aggression.”

Visual-Motor, Visual-Perceptual, and Fine Motor Outcomes in Very-Low-Birthweight Children at 5 Years.

Goyen, Lui, and Woods. Developmental Medicine and Child Neurology. 1998;40:76-81.

This study, from Westmead Hospital in NSW, Australia, of  83 “normal” preemies showed that 71% had below average fine motor skills. Twenty-three percent of these “normal” children were considered impaired or seriously impaired by these problems.

Neuropsychological  Analysis of the Visuomotor Problems in Children born Preterm at < or = 32 weeks of gestation: A Five Year Prospective Follow-up.”

Luoma, Herrgard, and Martikainen. Developmental Medicine and Child Neurology 1998;40:21-30.

This study, from Kuopio University Hospital in Finland, of 46 “normal” preemies showed that they achieved lower scores in visuospatial and sensorimotor functions compared to term born controls.

“They had most difficulty with drawing direction of lines and in integrating two or more forms.  They also had problems with 3-dimensional constructions as well as visual perception of rotated shapes or slopes of lines.”

Short-term Memory and Language Outcomes After Extreme Prematurity at Birth

Briscoe, Gathercole and Marlow. Journal of Speech, Language and Hearing Research. 1998:41:654-66. University of Bristol, England.

From the University of Bristol. 26 children born before 32 weeks gestation were compared with 26 fullterm children on short-term memory and language skills.  The preterm children scored more poorly across the full range of measures. 1/3 of the children showed large deficits and were classified as “at risk” for persisting language difficulties.

Psychological Findings in Preterm Children Related to Neurologic Status and Magnetic Resonance Imaging.”

Olsen, Vainionpaa, Paakko et al. Pediatrics.1998;102:329-36.

Magnetic Resonance Imaging of Periventricular Leukomalacia and its Clinical Correlation in Children.”

Olsen, Paakko, Vainionpaa et al. Annals of Neurology 1997;41:754-61

People often ask what an MRI can show about problems of prematurity.  These two studies that come from University of Oulu, Finland, and involve 42 “normal” children born <32 weeks and/or 1750 grams compared with term controls.  They show the following:

32% of the LBW and VLBW children showed signs of PVL

10% had CP, and all with CP had signs of PVL

31% of the preemies had “minor neurologic dysfunction” which showed up on such tests as “deviations in tongue movements,” “heel walking,” “Fogs test results (don’t know what this is), and finger opposition as well as behavioral disturbances. 25% of these children had evidence of PVL on MRI

However signs of PVL were also seen in 25% of preemie children considered normal.

No signs of PVL or CP were seen in control children who were born at term.

Children with PVL did worse on tests involving “heel walking” and on the “Fogs test”

Children who performed poorly on tests of visuoperceptual and spatial abilities often had signs of PVL, especially posterior ventricular enlargement.

Children who showed signs of “minor neurologic abnormalities” were likely to have attention problems (whether or not they had abnormal scans).  They also had the most trouble at school.

Although MRI abnormalities are often related to learning and behavior problems, the authors conclude that a thorough neurological examination is superior to MRI.  They recommend closer follow-up for children with minor neurological disorders.

The studies found that although MRI findings were often related to future problems they did not always predict learning and behavior problems. The authors suggested that thorough tests of neurological functioning were probably more useful.

Cerebral MRI of Very Low Birth Weight Children at 6 Years of Age Compared with the Findings at One Year

Skranes, Nilsen, Smevik et al. Pediatric Radiology. 1998;28:471-5.

“Cerebral Magnetic Resonance Imaging and Mental and Motor Function of Very Low Birth Weight Children at Six Years of Age.”

Skranes, Vik, Nilsen et al. Neuropediatrics. 1997;28:149-54.

In the next two studies researchers from University Hospital of Trondheim, Norway show that certain types of MRI abnormalities, which are extremely common even in “normal” preemies, are closely related to certain types of learning problems.

These two studies involve a one year geographical cohort of very low birth weight (VLBW, born weighing less than 1500 grams) children at age 6.  Of 31 VLBW non-disabled survivors, 27 were examined by MRI at age one and 20 of these were reexamined at age 6 and given various motor, IQ, and psychological/educational tests.

At age one 21 of the 27 infants (78%) had abnormal myelination on MRI. Myelination refers to the insulation of the nerve fibers with a fatty substance known as myelin.  Myelin helps conduct nerve impulses.  Many preemies show “delayed myelination,” and there is always the question with this finding of whether it reflects a true delay in myelination or whether it is an indication of permanent brain damage.

Most of the abnormal or “delayed” myelination in these children was located in the “central occipital white matter” and or in the “centrum semiovale” (it may help to get a map of the brain to get an idea precisely where these structures are located but they are in the area of the ventricles).

12 of the 27 (44%) of the “non-disabled” infants, at age one, had irregular and dilated ventricles.  Ventricular malformation and enlargement usually indicates that parts of the surrounding brain tissue have died and that the ventricles have enlarged to fill in the spaces.  This condition is sometimes referred to as “hydrocephalus ex vacuo.”  It is an indication of PVL (periventricular leukomalacia).  Only an estimated 30% of PVL is found on NICU ultrasound scans, so children who left the NICU with a clean bill of neurological health have often suffered undetected PVL (more about this when I review the study by Stewart et al).

Only two of the “non-disabled” VLBW preemies had normal scans at age 1.

At age 6, 20 of the 27 children were reexamined by MRI and other special tests to try to determine whether the abnormalities seen at age 1 had persisted and if so, what they meant.

Most of the children with abnormal MRIs at age 1 continued to have abnormal MRIs at age 6.

Children who had abnormal myelination in the central occipital white matter *combined with* abnormal myelination in the centrum semiovale and/or ventricular enlargement now showed signs of “gliosis” — or scarring related to tissue death and loss in glial cells of the brain. Glial cells are (I think) the cells that give support and structure to the neurons.  Gliosis is another indicator of PVL. 12 out of 13 children with these findings showed continued signs of PVL at age 6.

Abnormalities in the central occipital white matter alone had normalized in two children and persisted as delayed myelination in 3 children at age 6.

All the children with ventricular dilation (enlargement) at age 1 still had it at age 6.

In all, 12 of 20 (60%) of these non-disabled preemies had signs of gliosis (aka PVL).

The 20 children were then tested for IQ, motor, and perceptual functioning.

Gliosis in the centrum semiovale was related to lower scores on gross motor skills and locomotion.  Additional gliosis in the central occipital white matter was related to both fine motor and gross motor impairments.  The authors speculate that damage has occurred to both motor and visual pathways in these regions affecting eye-hand coordination and balance.

Overall presence of MRI abnormality was not related to lower IQ, however there was a significant relationship between gliosis [PVL] in both the centrum semiovale and the central occipital white matter and low scores on the performance part of the IQ test, as well as on tests of picture completion and the Block design test.  The authors state: “This may indicate visual and spatial perceptual problems, caused by damage to posterior visual pathways and occipito-thalamic tracts (get out your brain maps!)  dealing with visuo-motor integration.”

Executive Function of Children with Extremely Low Birthweight:  A Case Control Study

Harvey, O’Callaghan and Mohay. Developmental Medicine and Child Neurology. 1999;41:292-7.

The studies by Skranes and others indicate that *most* VLBW preemies have suffered white matter damage [PVL].  Recent research (not included in the packet) shows that white matter loss [PVL] can negatively affect gray matter development.  Gray matter is what makes up the frontal lobe, and the frontal lobe handles much of what is referred to as “executive function” — such
abilities as planning, sequencing, and inhibition of impulsive behavior.

This study from Mater Children’s Hospital in South Brisbane, Australia, tested 30 ELBW (<1000 g at birth) preemies at age 4 to 5 and compared their abilities with 30 fullterm children of the same age.  The preemies scored significantly lower than their peers on all executive tasks.

Behavioural Adjustments in School of Very Low Birthweight Children

Sykes, Hoy, Bill et al. Journal of Child Psychology and Psychiatry. 1997;38:315-25.

Not surprisingly, problems with “executive function” have consequences for school adjustment.  This study out of Queens University in Belfast, Northern Ireland, looked at a cohort of 243 prematurely born VLBW (<1500 g) children at age 7-8.  The children, both male and female, were rated by their teachers as expressing more behavioral and school adjustment problems that controls. Environmental factors such as high social class played no role in ameliorating these problems. The authors speculate that the problem behaviors “reflect a failure in self-regulatory [executive, or frontal lobe] functions.”

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