Endokrynologia Pediatryczna Pediatric Endocrinology

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1 Vol. 9/2010 Nr 3(32) Endokrynologia Pediatryczna Pediatric Endocrinology Evaluation of Auxologic Development in Children Born Small for Gestational Age Ocena rozwoju auksologicznego dzieci urodzonych ze zbyt niską masą ciała w stosunku do wieku płodowego 1 Małgorzata Szałapska, 1,2 Renata Stawerska, 1 Monika Tomaszewska, 1,3 Andrzej Lewiński, 1,2 Maciej Hilczer 1 Department of Endocrinology and Metabolic Diseases, Polish Mother s Memorial Hospital Research Institute, Lodz 2 Department of Paediatric Endocrinology, Medical University of Lodz 3 Department of Endocrinology and Metabolic Diseases, Medical University of Lodz Address for correspondence: Małgorzata Szałapska, Klinika Endokrynologii i Chorób Metabolicznych, Instytut Centrum Zdrowia Matki Polki, Łódź, ul. Rzgowska 281/289, tel/fax: , endo-iczmp@lodz.home.pl Key words: small for gestational age, prepubertal children, short stature, obesity, breast-feeding Słowa kluczowe: niska masa urodzeniowa, okres przeddojrzewaniowy, niskorosłość, otyłość, karmienie piersią The study was supported with the funds from the Ministry of Science and IT, Project No. 2751/P01/2007/32 STRESZCZENIE/ABSTRACT Introduction. Among children, born small for gestational age (SGA), two medical problems are observed: short stature and obesity. The aim of the study was assessment the frequency of short stature and obesity in prepubertal SGA children and the analysis of its reasons. Material and methods. 130 children (50 boys and 80 girls) born with low weight were analysed, aged from 4.7 to 9.7 years (mean ± SD: 6.8 ± 1.35 yr.). The following data were calculated: birth weight SDS, birth length SDS, actual height SDS, body mass index SDS (BMI SDS) and waist to height ratio (WHtR). Besides that, mother s diseases during pregnancy, perinatal complications and breast-feeding period data were also collected on. Results. Short stature was observed in only 3% of the children. A positive correlation between birth length SDS and height SDS was observed, but not between birth weight SDS and height SDS. The significantly higher HSDS values were found in the older subgroup (7 9.7 yr) vs. younger ( yr). Obesity was observed in 6.9% children, while the abdominal obesity in 16.15% children. If breast-feeding was continued more than 12 months, obesity in children was not observed. Conclusion. The incidence of short stature in prepubertal children with low birth weight is similar to that in the general population. An increased incidence of abdominal obesity is observed in prepubertal SGA children. Pediatr. Endocrinol. 9/2010;3(32): Wprowadzenie. Wśród dzieci urodzonych jako zbyt małe w stosunku do wieku ciążowego (small for gestational age, SGA) obserwowane są dwa główne problemy medyczne: niedobór wzrostu i otyłość. Celem pracy była ocena 29

2 Praca oryginalna Endokrynol. Ped., 9/2010;3(32):29-38 częstości występowania niedoboru wzrostu i otyłości w grupie dzieci urodzonych z SGA, a obecnie będących w okresie przeddojrzewaniowym (4 10 lat) oraz analiza czynników wpływających na wystąpienie powyższych powikłań. Materiał i metody. Badaniami objęto grupę 130 dzieci (50 chłopców i 80 dziewcząt) urodzonych ze zbyt niską masą ciała w stosunku do wieku ciążowego (SGA), będących obecnie w wieku od 4,7 do 9,7 lat (średnia ± SD: 6,8 ± 1,35 lat). Obliczono następujące parametry: SDS urodzeniowej masy ciała (BW SDS), SDS urodzeniowej długości ciała (BL SDS), SDS obecnego wzrostu (HSDS), wskaźnik masy ciała (BMI) oraz BMI SDS, jak również współczynnik talia:wzrost (WHtR). Poza tym zebrano dane dotyczące występowania chorób podczas ciąży u matki, powikłań okołoporodowych oraz czasu trwania karmienia naturalnego. Wyniki. W analizowanej grupie dzieci z SGA niedobór wzrostu był obserwowany jedynie u 3% pacjentów (HSDS poniżej -2,0). Stwierdzono istotną statystycznie dodatnią korelację pomiędzy długością urodzeniową (BL SDS) a obecnym wzrostem (HSDS), natomiast nie obserwowano takiej zależności pomiędzy masą urodzeniową (BW SDS) a obecnym wzrostem (HSDS). Znamiennie wyższe wartości HSDS obserwowano w podgrupie dzieci starszych (7,0 9,7 lat) niż młodszych (4,7 6,9 lat). Jeśli chodzi o otyłość (BMI SDS powyżej +1,7), to stwierdzono ją u 6,9% dzieci, przy czym otyłość brzuszna (WHtR powyżej 0,5) była rozpoznana u większej liczby dzieci aż 16,15% całej grupy. W grupie dzieci karmionych naturalnie dłużej niż 12 miesięcy otyłość nie była obserwowana w ogóle. Wnioski. Częstość występowania niedoboru wzrostu u dzieci urodzonych ze zbyt niską masą ciała w stosunku do wieku ciążowego jest zbliżona do częstości występowania niedoboru wzrostu w populacji ogólnej. U dzieci z SGA już w okresie przeddojrzewaniowym obserwuje się wysoką częstość występowania otyłości brzusznej. Endokrynol. Ped. 9/2010;3(32): Introduction Among children, born small for gestational age (SGA), two different main health problems are observed: short stature and obesity. In about 10 15% of SGA children, no catch up growth phenomenon is observed by the 4 th year of age and most of these children continue poor growth through their childhood, eventually becoming short adults [1, 2]. It is estimated that the relative risk for short stature in adulthood is at 5.2 for the SGA children, which are born too light, and 7.1 for those, born too short [3]. Since growth hormone deficiency (GHD) is rather rare in this group of patients, it is the pulsatile GH secretion disorders or receptor or post-receptor disturbances, concerning both the structure and secretion of IGF-I, which may probably be at the base of the no-catch up phenomenon [4, 5]. On the other hand, SGA individuals may present with decreased lean body mass and central adiposity, which put them at risk of long-term morbidity, related to insulin resistance and metabolic disease. These complications are observed even before the third decade of life [1]. They are most probably associated with impaired blood supply to the pancreas during foetal life, resulting in a too low secretion of insulin in that period. Normal or excessive nutrition after birth can induce obesity in those children, as well as insulin resistance and metabolic syndrome, with all their consequences in adult life (cardiological and metabolic complications and diabetes mellitus type 2). However, the above-mentioned disorders are not found in all SGA children. Therefore, it is necessary to identify these patients with SGA out of the entire SGA population who will require constant endocrinological care. The goal of the reported study was an evaluation of auxological development in SGA children, born at the Polish Mother s Memorial Hospital Research Institute (PNNH-RI) in Lodz during the years , and an identification of those patients, who for their growth failure or overweight and obesity, including its visceral type required endocrinological care. It seems that such an early selection of cases, which may later on demand further endocrinological care, can minimise the incidence of metabolic disorders at later stages of life. An identification of children with persistent growth failure after the 4 th year of life will indicate the necessity of GHD diagnostics. Children with GHD require GH therapy, while children with short stature, persistent after the age of 4, however, with excluded GHD, also require constant medical follow up but in Poland, so far, no GH therapy as the rule has been recorded for the cases of non-ghd short children born small for gestational age. Material and methods The study protocol had been approved by the Local Commission of Ethics. Using the database of the Polish Mother s Memorial Hospital Research Institute in Łodz, which is a 3 rd degree reference centre for perinatal care, written invitations were sent to the parents of the children, born during the 30

3 period of and with birth weight < 2500 g. Those invitations were responded by parents of more than 150 children, which then attended the Endocrinological Outpatient Clinic of the Polish Mother s Memorial Hospital Research Institute (the attendance rate at approximately 65%). Out of the children, which responded the invitation, only those cases were qualified, where birth weight (BW) was below -2.0 SD for the gestational age (GA) and gender (premature children with birth weight below 2500 g, but appropriate for GA were not enrolled into the study). Also twins and children with congenital malformations were excluded from the study. In the analysed group of children, neither Silver-Russel s nor Turner s syndrome cases were noted. A group of 130 children (50 boys and 80 girls) entered the study, which are now at the age between 4.7 and 9.7 years (the mean ± SD: 6.8 ± 1.35 yr). Following the data from health record books, BW SDS and BL SDS (birth weight and length referred to GA) were determined, vs local population data [6]. During control visits, the patients height was measured on a stadiometer, with height standard deviation score (HSDS) determination vs local population standards [7]. Moreover, body weight of the children was evaluated and body mass index (BMI) and BMI standard deviation score (BMI SDS) were determined vs local population data [7]. Short stature was recognised when HSDS was below -2.0; obesity was diagnosed when BMI SDS was more than +1.7 (value for the 90 th percentille). Waist circumference was measured in each child and the waist-to-height (WHtR) ratio was calculated. Following the data for the population of Polish children, as presented by Nawarycz and Nawarycz [8], visceral obesity was identified, when WHtR was more than 0.5. Based on the history, obtained from parents and/ or guardians of the child and on data from health record books, beside gestation duration, data were also collected on mother s diseases during pregnancy, the way of delivery, birth health evaluation by Apgar score and breast-feeding period. The prevalence rates of short stature and obesity, including visceral obesity, were analysed in the studied group of children. Then the patients were divided into two (2) age groups and submitted to a comparative analysis, regarding the studied parameters. The prevalence of obesity and short stature was analysed, referring it to the actual age of examined children, their gender, birth weight and length, delivery way, birth Apgar score, mother s diseases during gestation and breast-feeding period. Statistical analysis. Pearson s correlation coefficient was used in the evaluation of results, obtained from studied on the entire population The data were statistically analysed, using the one-way analysis of variance (ANOVA), followed by post-hoc testing of the differences of means (RIR Tukey test). In case of abnormal distribution of variables, the non-parametric Mann-Whitney U test was used for a screening evaluation of the differences of means. Statistical significance was determined at the level p < Results In the analysed group, birth weight of the children varied from to -2.0 SD. Concomitant deficit of body length (symmetric suppression of intrauterine development) was found in 11 children; prematurity was the case in 7. In 10 mothers, significant diseases were noted during pregnancy, including gestosis (9 cases) and severe anaemia (1 case). Only five (5) children were born in asphyxia, nevertheless, the cesarean cut was performed in 51 mothers. Natural feeding was used < 6 weeks in 41 children and > 12 months in 26 children. Table I presents data, concerning the evaluation of auxological development parameters, both after birth and at examination time. No statistically significant, gender-related differences were found in the analysed parameters. Neither was there any statistical correlation between BW SDS and: HSDS, BMI SDS and WHtR values in the analysed group of children, while a significant correlation was found between BL SDS and HSDS (r = 0.30, p < 0.05); no such correlation was observed between BL SDS and BMI SDS or between BL SDS and WHtR. Short stature was found in 4, out of 130 children (3.07%), with 1 case of premature birth (in the 33 rd week) with symmetric BW an BL deficits, while in the other 3 cases, growth deficit was observed in children born in term and with normal body length. The distribution of HSDS values was close to normal in the study group, with body height below the mean level found in merely 46% of the children and body height above the mean level in 54% (see Figure 1). In conformity with the earlier presented, statistically significant positive correlation between 31

4 Praca oryginalna Endokrynol. Ped., 9/2010;3(32):29-38 Table I. Data of the perinatal period and the actual auxological parameters of children, born with SGA, depending on child s gender Tabela I. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w zależności od ich płci girls 80 boys 50 N= GA (weeks) BW SDS BL SDS HSDS BMI SDS ± ± ± ± ± ± ± ± ± ± 0.95 Waist to height ratio (WHtR) 0.46 ± 0.05 p p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 Fig. 1. Distribution of HSDS feature in the analysed population of children born small for gestational age (SGA) Ryc. 1. Rozkład cechy HSDS w analizowanej populacji dzieci urodzonych z niską masą ciała (SGA) Fig. 2. Comparision of actual body height (expressed by HSDS values) of children born with symmetric and asymmetric intrauterine growth retardation Ryc. 2. Porównanie obecnego wzrostu (wyrażonego wartością H SDS) dzieci urodzonych z symetrycznym i asymetrycznym typem wewnątrzmacicznego zahamowania wzrastania BL SDS and HSDS, the children with symmetric SGA presented with significantly lower HSDS values vs those with asymmetric SGA (too low birth weight with normal body length; Table II, Figure 2). Having divided the analysed group into younger ( years) and older ( years) children, significantly higher HSDS values were found in the group of older children vs that with younger children (see Table III), what indicates the growth rate improvement with age in the prepubertal period (see Figure 3). In turn, taking into account increased BMI SDS values in the analysed group of patients, obesity was identified in 9 (6.9%) children. The distribution of BMI SDS values in the studied population was also close to normal (see Figure 4). Abdominal obesity was diagnosed in 21 children (16.15%), out of which, in 8 cases, it accompanied the obesity, identified from BMI SDS values and in the 13 remaining cases, abdominal obesity was observed in children with normal BMI SDS values (below +1.7 SD). Also, BMI SDS values were higher in the group of older children vs those in younger children, however, the differences were not statistically significant (see Table III, Figure 5). No significant differences were found between the age groups with regards to the WHtR (see Table III). No significant correlations were found, concerning the actual parameters of body weight and height (BMI SDS and H SDS) of the children and pregnant mother s diseases, pregnancy duration or way of delivery (see Tables IV and V). Nevertheless, lower birth weight was noted in the children from mothers with chronic diseases during pregnancy. In turn, significantly lower BMI SDS and WHtR values were found in the children, breast-fed for periods more than 12 months vs the children either breast-fed 32

5 Table II. Data of the perinatal period and the actual auxological parameters of children, born with SGA, depending on birth length Tabela II. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w zależności od urodzeniowej długości ciała Low birth length Normal birth length N = GA (weeks) BW SDS BL SDS HSDS BMI SDS ± ± ± ± ± ± ± ± ± ± 1.04 Waist to height ratio (WHtR) ± p p > 0.05 p >.05 p < 0.05 p < 0.05 p > 0.05 p > 0.05 Table III. Data of the perinatal period and the actual auxological parameters of children born with SGA in particular age groups Tabela III. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w poszczególnych grupach wiekowych N = GA (weeks) BW SDS Birth length (BL) (cm) HSDS BMI SDS Waist to height ratio (WHtR) Younger children (age 5-7 yr) ± ± ± ± ± 1.18 Older children (age 7-9 yr) ± ± ± ± ± 0.90 p p > 0.05 p > 0.05 p > 0.05 p < 0.05 p > 0.05 p > 0.05 Fig. 3. Comparison of the actual body height (expressed by HSDS values) in the younger and older children from analysed group of patients born small for gestational age (SGA) Ryc. 3. Porównanie obecnego wzrostu (wyrażony wartością HSDS) młodszych i starszych dzieci z analizowanej grupy pacjentów urodzonych z niską masą ciała (SGA) Fig. 4. Distribution of BMI SDS feature in the analysed population children born small for gestational age (SGA) Ryc. 4. Rozkład cechy BMI SDS w analizowanej populacji dzieci urodzonych z niską masą ciała (SGA) 33

6 Praca oryginalna Endokrynol. Ped., 9/2010;3(32):29-38 Table IV. Data of the perinatal period and the actual auxological parameters of children born with SGA, depending on the prevalence of diseases in mother during pregnancy Tabela IV. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w zależności od występowania chorób u matki w trakcie trwania ciąży Gestation complicated by mother s diseases Gestation without complications N = GA (weeks) BW SDS BL SDS HSDS BMI SDS ± ± ± ± ± ± ± ± ± ± 1.10 Waist to height ratio (WHtR) 0.46 ± 0.03 p p > 0.05 p < 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 Table V. Data of the perinatal period and the actual auxological parameters of children born with SGA, depending on delivery type Tabela V. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w zależności od sposobu rozwiązania ciąży Natural birth 79 Caesarean cut 51 N = GA (weeks) BW SDS BL SDS HSDS BMI SDS ± ± ± ± ± ± ± ± ± ±1.17 Waist to height ratio (WHtR) ± ±0.04 p p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 Fig. 5. Comparison of the actual body weight (expressed with BMI SDS values) in the younger and older children from analysed group of patients born small for gestational age (SGA) Ryc. 5. Porównanie obecnej masy ciała (wyrażonej wartością BMI SDS) u młodszych i starszych dzieci z analizowanej grupy pacjentów urodzonych z niską masą ciała (SGA) for shorter periods or not breast-fed at all (see Table VI). In the group of 26 children, breastfed for periods more than 12 months, abdominal obesity was found in 1 case only, while no increased BMI SDS values were observed in any of the children. In prepubertal children, born with low body weight, short stature, persisting after 4 years of life, is observed in only 3% of the patients. Moreover, in the studied group of children, a gradual improvement in growth rate (expressed by HSDS values) is observed at the age of 4 10 years. However, a positive correlation between birth length and the child s body height at the age of 4 10 years was observed. In prepubertal children, born with low birth weight, the obesity, expressed by BMI SDS values, is observed in 6.9% of the patients, while the abdominal obesity, determined by WHtR, is found in 16.15% of the children. In children with SGA, a gradual increase of relative body weight 34

7 Table VI. Data of the perinatal period and the actual auxological parameters of children born with SGA, depending on the period of natural feeding Tabela VI. Dane dotyczące okresu okołoporodowego oraz obecnych parametrów auksologicznych w analizowanej grupie dzieci urodzonych z niską masą ciała (SGA) w zależności od czasu trwania karmienia naturalnego Breast feeding < 12 months Breast feeding > 12 months N = GA (weeks) BW SDS BL SDS HSDS BMI SDS ± ± ± ± ± ± ± ± ± ± 0.76 Waist to height ratio (WHtR) 0.45 ± 0.03 p p > 0.05 p > 0.05 p > 0.05 p > 0.05 p < 0.05 p < 0.05 (expressed by BMI SDS) is observed in subsequent years during the age of 4 10 years. Breast-feeding seems to reduce the risk for obesity in SGA children, especially if it is continued for a period of time more than 12 months. Discussion Although it is known that a child with birth weight and/or birth length below the lower limits of the reference values for GA and sex, is regarded as a child born small for gestational age (SGA), low birth weight was the main criterion in the reported study. It was a consequence of the common availability of this parameter in the database of the Polish Mother s Memorial Hospital Research Institute. In result of that approach, no children with normal body weight and decreased body length were accounted for in our analysis. It could be seen as an obvious defect of the study if not the fact that body length measurements at birth are seriously error-laden, acc. to some authors, up to 5 cm [9]. Nevertheless, children with too low body length should also be attended in everyday practice with particular care, especially in the light of the fact that persistent growth deficit after the age of 4, is more frequently observed just in the children with small body length at birth [3]. Since low birth weight was the main criterion in our analysis, the number of children concomitantly too short (i.e., with symmetric SGA) was merely 11, out of 130. With such a small group of children with SGA, the prevalence of persistent short stature after the age of 4 in the study group was in fact 3%. As it is known from the literature, the catch up phenomenon after the 2 nd year of life is not revealed by approximately 10 15% of children with SGA [1, 2]. It is also known that in premature children, the catch up may occur later, nevertheless, not later than till the 4 th year of life [1,2]. In the studied population of children with SGA, born at the Polish Mother s Memorial Hospital Research Institute in Łódź during the years , the prevalence of growth deficit after the 4 th year of life was lower than expected. Since the recruitment of children into the study was letter-supported, with written invitations sent to all the parents with children born during the years in question at the PMMH-RI in Łódź, with birth weight < 2500 g, and the rate of attendance (i.e., the rate of response) by those children was approximately 65%, it can be assumed that the data are slightly lowered. On the other hand, it would seem logical that the invitations should have been responded especially by those parents whose children faced some health problems. It could also be possible that some of the children with short stature, born during the same period of time, had already been receiving specialist care, what could explain the disregard of our invitation by their parents. On the other hand, it is known that the lack of catch-up phenomenon is more frequently observed in children with too small body length. Regarding 11 such children in our analysis, persistent growth deficit was observed in 1 child only (i.e., 9.1%). Nevertheless, it seems that the general health care improvement, observed in the early stages of newborn s and infant s life, especially that, related to proper nourishment of children, born at a perinatal care reference centre of the 3 rd degree, reduces the incidence of no catch up phenomenon in this group of patients, with disorders of the GH-IGF-I axis functionality to be regarded as the only cause of growth failure. 35

8 Praca oryginalna Endokrynol. Ped., 9/2010;3(32):29-38 Moreover, in the analysed population of children, we observed a continuous improvement of HSDS with age. That would suggest that, in certain cases, it could be appropriate to extend the observation period of growing rate up to the 6 th, or even to the 8 th year of life, before the lack of catch up phenomenon is identified in a child with SGA, qualifying such a child to consideration of growth hormone therapy. It is known that the children, born with SGA, in which the catch up phenomenon occurs with regards to both body weight and height, a tendency is observed towards obesity development in early childhood. The incidence rate of obesity in the population of children in Poland concerns approximately 10 15% of the children till the 10 th year of life [10] and is similar to the incidence rates, observed in other European countries. In the analysed group of patients, we noted an increased prevalence of abdominal obesity, which affected as many as 16% of children. Other authors have reported similar observations. In 2008, Ibanez et al. [11, 12] reported an increased incidence of abdominal obesity in children with SGA, observed already in the 6 th year of life. In an earlier paper, we demonstrated a high degree of compatibility between the evaluated volume of adipose tissue in children by means of bioimpedance study and the WHtR [13]. It seems then that the measurement of waist circumference and its juxtaposition with child growth is a simple diagnostic tool to identify the majority of cases of abdominal obesity in children and to apply prophylactic measures to avoid its unfavourable effects for the child. It seems also that, regarding children with SGA, long-term breast feeding is worth recommending. Taking into account the known fact that a rapid increase of body weight and length in a child with SGA, observed in an early period of life, is associated with an increased risk for the metabolic syndrome, insulin resistance, diabetes mellitus type 2, hypertension and coronary heart disease in later life [15, 16, 17], breast feeding is to be promoted in these children in order to avoid their overfeeding with highly caloric food. Conclusions 1. The incidence of short stature after the 4 th year of life in prepubertal children with low birth body weight is not higher than in the general population (about 3%). 2. Lower growth rate of a child in prepubertal age is mainly related to short body length at birth. 3. In children with SGA, there is a tendency towards an improvement of growth percentille position in subsequent years after the 4 th year of life. 4. An increased incidence of abdominal obesity is observed in prepubertal children with SGA. 5. Breast feeding for more than 12 months reduces the risk for obesity and abdominal obesity in children with SGA during the 1 st decade of their life. REFERENCES/PIŚMIENNICTWO [1] Saenger P., Czernichow P., Hughes I. et al.: Small for gestational age: short stature and beyond. Endocr. Rev., 2007:28, [2] Clayton P.E., Cianfarani S., Czernichow P. et al.: Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J. Clin. Endocrinol. Metab., 2007:92, [3] Albertsson-Wikland K., Karlberg J.: Postnatal growth of children born small for gestational age. Acta Paediatr. Suppl., 1997:423, [4] Boguszewski M., Rosberg S., Albertsson-Wikland K.: Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children. J. Clin. Endocrinol. Metab., 1995:80, [5] Verkauskiene R., Jaquet D., Deghmoun S. et al.: Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood. J. Clin. Endocrinol. Metab., 2005:90, [6] Malewski Z., Słomko Z., Klejewski A.: Relacja wieku ciążowego i masy urodzeniowej noworodków z regionu Wielkopolski. Materiały I Kongresu Medycyny Perinatalnej, 1995, [7] Palczewska I., Niedźwiecka Z.: Wskaźniki rozwoju somatycznego dzieci i młodzieży warszawskiej. Medycyna Wieku Rozwojowego, 2001:5(supl 1/2), [8] Nawarycz T., Ostrowska-Nawarycz L.: Visceral obesity in children and youth experience from the city of Łódź. Endokrynol. Otyłość i Zab. Przemiany Materii, 2007:3, 1-8. [9] Wollmann HA.: Intrauterine growth restriction: definition and etiology. Horm. Res., 1998:49 (Suppl 2),

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