Postnatal growth restriction in low birth weight infants is associated with long term adverseneuro-developmental sequel. Meanwhile, infants with excessive weight gain in early weeks oflife have a greater likelihood of later obesity, cardiovascular disease, and diabetes. Identifyingfactors associated with acceptable growth rate in low birth weight infants is important toprevent this potential long term morbidity. The aim of this study was to identify factors associatedwith acceptable growth rate in low birth weight infants. Prospective cohort study was conductedamong 73 low birth weight infants. Growth rate of these infants was determined by serialweight measurement during perinatal care and after being discharged until 46 – 50 weeks postmenstrual age. Growth rate was considered normal if average daily weight gain is 10 – 20 g/kg/day. Factors associated with this acceptable growth rate were analyzed by univariate andmultivariate statistical analysis. Normal growth rate was found in 62.7% subjects (42/67).Significant rate difference of average daily growth was found between small for gestational age(SGA) infants and appropriate for gestational age (AGA) infants (mean difference -2.90 g/kg/day; 95%CI: -5.68 - -0.12). The SGA infants had a greater risk for gaining weight below acceptablegrowth rate (adjusted RR= 2.9; 95%CI: 1.1 – 8.5). In conclusion, SGA is the only factor whichcan be associated with normal growth rate in low birth weight infants. Moreover, SGA infantsare in a greater risk for having slower growth rate compared to AGA.Keywords: growth rate - post natal - low birth weight – prognostic - gestational rat

Setya Wandita, Kristia Hermawan Djauhar Ismail

English

Journal of the Medical Sciences (Berkala ilmu Kedokteran)

72J Med Sci, Volume 44, No. 1, March 2012: 72 - 77iVolume 44, No. 1, March 2012: 72 - 77* corresponding author: dr.kryzt@gmail.comPrognostic factors for normal postnatalgrowth rate in low birth weight infantsKristia Hermawan, Djauhar Ismail, Setya WanditaDepartment of Pediatrics, Faculty of Medicine, Universitas Gadjah Mada/Dr. SardjitoGeneral Hospital, Yogyakarta, IndonesiaABSTRACTPostnatal growth restriction in low birth weight infants is associated with long term adverseneuro-developmental sequel. Meanwhile, infants with excessive weight gain in early weeks oflife have a greater likelihood of later obesity, cardiovascular disease, and diabetes. Identifyingfactors associated with acceptable growth rate in low birth weight infants is important toprevent this potential long term morbidity. The aim of this study was to identify factors associatedwith acceptable growth rate in low birth weight infants. Prospective cohort study was conductedamong 73 low birth weight infants. Growth rate of these infants was determined by serialweight measurement during perinatal care and after being discharged until 46 – 50 weeks postmenstrual age. Growth rate was considered normal if average daily weight gain is 10 – 20 g/kg/day. Factors associated with this acceptable growth rate were analyzed by univariate andmultivariate statistical analysis. Normal growth rate was found in 62.7% subjects (42/67).Significant rate difference of average daily growth was found between small for gestational age(SGA) infants and appropriate for gestational age (AGA) infants (mean difference -2.90 g/kg/day; 95%CI: -5.68 - -0.12). The SGA infants had a greater risk for gaining weight below acceptablegrowth rate (adjusted RR= 2.9; 95%CI: 1.1 – 8.5). In conclusion, SGA is the only factor whichcan be associated with normal growth rate in low birth weight infants. Moreover, SGA infantsare in a greater risk for having slower growth rate compared to AGA.ABSTRAKHambatan pertumbuhan postnatal bayi berat lahir rendah berhubungan dengan luaran neurologisjangka panjang yang jelek. Sementara itu, pertambahan berat badan yang berlebihan pada awalkehidupan meningkatkan risiko obesitas, penyakit kardiovaskular, dan diabetes di kemudian hari.Identifikasi faktor-faktor yang berkaitan dengan laju pertumbuhan normal pada bayi berat lahirrendah penting untuk mencegah potensi timbulnya morbiditas jangka panjang tersebut. Penelitianini bertujuan untuk mengidentifikasi faktor-faktor yang berhubungan dengan laju pertumbuhannormal pada bayi berat lahir rendah. Penelitian kohort prospektif dilakukan terhadap 73 bayiberat lahir rendah. Laju pertumbuhan bayi diukur dengan penimbangan berat badan bayi secaraserial selama perawatan perinatal dan setelah keluar dari rumah sakit sampai umur 46-50 minggupost menstruasi. Laju pertumbuhan dinilai normal bila rerata pertambahan berat badan berkisar10-20 g/kg/hari. Faktor-faktor yang berhubungan dengan laju pertumbuhan dianalisis secaraunivariat dan multivariat. Laju pertumbuhan normal ditemukan pada 62,7% subyek (42/67).Ditemukan perbedaan yang bermakna laju pertumbuhan harian antara bayi kecil masa kehamilan(KMK) dan bayi sesuai masa kehamilan (SMK) (beda rerata -2,90 g/kg/hari; 95%CI: -5,68 - -0,12).Bayi KMK memiliki risiko lebih tinggi untuk mengalami pertambahan berat badan di bawahnormal (adjusted RR 2,9; 95%CI: 1,1–8,5). Dapat disimpulkan KMK merupakan satu-satunyafaktor yang berhubungan dengan laju pertumbuhan normal pada bayi berat lahir rendah. BayiKMK memiliki risiko lebih tinggi untuk mengalami laju pertumbuhan lebih lambat dibandingkandengan bayi SMK.Keywords: growth rate - post natal - low birth weight – prognostic - gestational rate73Hermawan et al., Prognostic factors for normal postnatal growth rate in low birth weight infantsINTRODUCTIONGrowth is an essential component in healthsurveillance of low birth weight (LBW) infants,because almost any problem within physiologic,interpersonal and social domains can adverselyaffect growth. Growth monitoring is particularlyimportant to enable early detection of growthdisorders. Several studies have shown thatpostnatal growth restriction in low birth weightinfants is associated with long term adverseneuro-developmental sequel.1,2Casey et al.2 found that small for gestationalage (SGA) infants with normal postnatal growthdid not differ from the appropriate forgestational age (AGA) infants in cognitive,behavioral, or academic achievement at age 8,while SGA infants with postnatal failure tothrive had the lowest cognitive scores andacademic achievement. Meanwhile, in the earlyweeks of life, infants with excessive weight gainhave a greater likelihood of later childhood andadult obesity, cardiovascular disease, anddiabetes.3-5 Aprospective cohort study revealedthat children who showed catch-up growthbetween zero and two years were fatter and hadmore central fat distribution at five years thanother children.3It appears that rapid gain in the first monthmay have long-term negative consequences.6Thus, identifying factors associated withacceptable growth rate in low birth weight infantare important to prevent this potential long termmorbidity. This study was aimed to identifyfactors associated with acceptable growth ratein low birth weight infant within 50 weeks postmenstrual age.MATERIALS AND METHODSStudy populationThis was a prospective cohort studyinvolving LBW infants admitted to perinatalward, Dr. Sardjito General Hopital inYogyakarta between September and December2011. Any infants, whose birth weight werebetween 1500 and 2499 gram, with no majorcongenital anomaly, had undergone prenatal careand were discharged according to medicalconsiderations, were eligible for this study. Weexcluded any infants who had potential growthimpairment due to several clinical conditionssuch as congenital heart disease, broncho-pulmonary dysplasia, maternal HIV infection,malignancy and feeding problem. Subject wasalso excluded if written consent from parentsfailed to obtain or was unreachable by phonefor periodic monitoring. The protocol of thestudy has been approved by the Medical andHealth Research Ethics Committee, Faculty ofMedicine, Universitas Gadjah Mada.Data collectionTo monitor weight gain, we weighed theinfants everyday during hospitalization. Afterbeing discharged, monthly weight gain datawere obtained from parental reporting by phonecall. Subjects were followed until 46 to 50weeks post menstrual age, in which the growthreference chart remains linear during thisperiod. 7 Growth rate was calculated bycomparing the amount of weight gain (gram) andtime unit to obtain that weight increment (days).Growth rate was considered as normal ifaverage daily weight gain was 10 – 20 g/kg/day.8 Factors associated with growth rate wererecorded i.e. small for gestational age (SGA),gestational age, breastfed, maternal education,maternal occupation and socioeconomic level.Infants were considered as SGA if their birthweight was below the 10th percentile of meanweight for gestational age; infants with birthweight between 10 th – 90th percentile wascategorized as appropriate for gestational age(AGA). Infants were categorized as preterm ifthe gestational age was less than 37 weeksgestation. Socioeconomic level was determined74J Med Sci, Volume 44, No. 1, March 2012: 72 - 77based on family income; when the family incomewas lower than minimal standard province salary,it would be categorized as low socioeconomiclevel. Infants were categorized as fully breastfedif they only got breastfed with no other nutritionalsubstances beside pre-lacteal feeding that beengiven during perinatal care.Statistical analysisPearson chi square test was used to comparedistributions of each prognostic factors, two tailedp values of less than 0.05 were set to indicatestatistical significance. All variables withsignificance level less than 0.15 in univariateanalysis were subjected to multivariable logisticregression model. Relative risk with 95% CI wascalculated for each factor.RESULTSThere were 77 LBW infants who met theinclusion criteria, four infants were excluded;three of them unreachable by phone and oneinfant born from mother with HIV infection. Sixsubjects were lost to follow up, leaving 67subjects for final analysis. TABLE 1 presentsthe baseline characteristic of the subjects.During perinatal care, most infants (85%)showed suboptimal growth rate. Normal growthrate was found in only 15% (11/73) infants. Atpost discharged period, 70% (47/67) infantscould attain normal growth rate. Overall,TABLE 1. Baseline characteristics of the infantsenrolled in the studyaverage daily weight gain was normal in 63%(42/67) infants.The distribution of variables by post natalgrowth rate achievement within 46 – 50 weekspost menstrual age is presented in TABLE 2,whereas the prognostic factors for normalgrowth rate based on multivariate analysis arepresented in TABLE 3. This study found thatSGA and socioeconomic level were factorswhich influence normal growth rate among LBWinfants. However, further multivariate analysisusing logistic regression showed that just SGAthat influence normal post natal growth rate(TABLE 3). The SGA infants had growth rateless than 10 g/kg/day within 46-50 weeks postmenstrual age 3.3 time higher thanAGAinfants.75Hermawan et al., Prognostic factors for normal postnatal growth rate in low birth weight infantsTABLE 2. Distribution of variables by post natal growth rate achievement within 46 – 50 weekspost menstrual ageTABLE 3. Prognostic factors for normal growth rate based on multivariate analysisDISCUSSIONSeveral studies have shown that most ofLBW infants will regain their weight at earlylife.9,10 A cohort of 133 full-term, LBW infantsfrom poor families in Brazil showed thatincrement of weight was clearly seen during thefirst 8 weeks of life. Between birth and 12months of age, 90.2% LBW infants hadimproved in weight-for-age z-scores (WAZ).The estimated median age at WAZ peak was 77days (interquartile range 65–90 days).11 In thisstudy it was found that more than 60% of LBWinfants had an acceptable growth rate within 46– 50 weeks post menstrual age.Other studies have also demonstrated thatmost preterm SGA children who ultimatelygrow into normal range for population willdemonstrate significant compensatory growthwithin the first year of life, and that the likelihoodof such compensation diminishes after that age.12This tendency to catch back to normal isinfluenced by the size at birth and degree ofprematurity, VLBW SGAinfants have a greaterchance of never catching back toward normalover time. In contrast, the growth pattern of thelarger LBWPT infants shows that their size tendsto return close to the reference size of normalbirth weight term infants in the first years oflife.13 In this study it was found that SGA infants76J Med Sci, Volume 44, No. 1, March 2012: 72 - 77had significantly lower average daily weightgain compared toAGAinfants (mean difference-2.90 g/kg/day; 95% CI: -5.68 - -0.12).Prospective study which enrolled 818preterm infants in the Infant Health andDevelopment Program (IHDP) who werestudied from birth to 36 months of correctedage showed that preterm SGA infantsdemonstrated decreasing weight-gain velocitycompared with preterm infants with AGA until40 weeks of corrected age. Heights and weightsof infants with either symmetric or asymmetricintrauterine growth retardation remainedsignificantly retarded compared with AGApreterm patients and the National Child HealthSurvey (NCHS) reference population. Preterminfants with both symmetric and asymmetricgrowth retardation demonstrated limited catch-up growth in weight until age 4 months and thenparalleled the AGA preterm patients and theNCHS reference population.14 This finding isin line with this study which found that SGAinfants tend to attain growth rate bellowacceptable average daily weight gain.Nutritional supplementation during earlyinfancy may be of particular importance forinfants with on-going additional metabolicrequirements. Several strategies for increasingnutrient delivery for preterm infants followinghospital discharge are available. However, untilnowadays there are limited data fromrandomized controlled trials to determinewhether feeding preterm infants followinghospital discharge with nutrient-enrichedformula milk versus human breast milk affectsgrowth and development.15,16 Review from seventrials which recruited a total of 631 infants alsodoes not provide strong evidence that feedingpreterm infants following hospital dischargewith nutrient-enriched formula compared withstandard term formula affects growth rates ordevelopment up to 18 months correctionalages.17 It was also found that proportion ofinfants with normal growth rate in LBW infantswho were fully breastfed and in LBW infantswho got additional formula milk were notsignificantly different.Maternal behaviors are related to thegrowth of term and premature infants, althoughthe mechanism through which this occurs isunclear. Maternal behaviors which wereassessed using home visits with global ratingsof Warm Sensitivity and Punitiveness indicatedthat higher levels of maternal Punitiveness wererelated to slower rates of physical growth inpreterm infants.18 This study failed to prove thatmaternal factor, which assessed based oneducation level and occupation, was one ofprognostic factors for normal growth rateattainment in low birth weight infants.An epidemiological study which exploredthe impact of socio-economic status on postnatalgrowth showed that poverty, as measured byhouse rate-able value, was associated withweight gain during the first year of life.19Longitudinal study which intensively monitored133 LBW infants living in poor socioeconomicconditions in northeast Brazil also found that ina multivariate model, socio-economic variablesresponsible for the variation in maximum gainin weight-for-age z-score achieved during the12-month period.11 In this study, socio-economiclevel which was determined by family incomedid not significantly affect normal growth rateamong LBW infants. This finding needs to bereconsidered because family income did notmerely reflect poverty.The present study has several limitations.During post discharged period, body weight datawere obtained using non-standardizedmeasurement methods using many differentweight scales. This may affect measurementprecision. We relied on maternal reporting offirst day of the last menstruation period toestimate gestational age thus recall bias mayoccur, but we validated this estimation byperforming Dubowitz scoring methods.77Hermawan et al., Prognostic factors for normal postnatal growth rate in low birth weight infantsCONCLUSIONIn conclusion, this study shows that SGA isthe only factor associated with normal growthrate in low birth weight infants. Infant beingSGA had a greater risk of having slower growthrate within 50 weeks post menstrual age.ACKNOWLEDGEMENTSAuthors would like to thank all infants andtheir parents who participated in this study. Wealso thank Head of Department of Department ofPediatric,FacultyofMedicine,UniversitasGadjahMada/Dr. Sardjito General Hospital,Yogyakarta,Indonesia for his permission to conduct this study.REFERENCES1. Cooke RWI, Foulder-Hughes L. Growthimpairment in the very low preterm and cognitiveand motor performance at 7 years. Arch Dis Child2003; 88(6):482-7.2. Casey PH, Whiteside-Mansell L, Barrett K.Impact of prenatal and postnatal growth problemsin low birth weight preterm infants on school-ageoutcomes: an 8-year longitudinal evaluation.Pediatrics 2006; 118(3):1078-86.3. Ong KL, Ahmed ML. Emmett PM, Preece MA,Dunger DB. Association between postnatal catchupgrowth and obesity in childhood: prospective cohortstudy. Br Med J 2000; 320(7240):967–71.4. Regan F, Cutfield WS, Jefferies C. The impact ofearly nutrition in premature infants on laterchildhood insulin sensitivity and growth.Pediatrics 2006; 118(5):1943-9.5. Eriksson JG, Forsen T, Tuomilehto J. Early growthand coronary disease in later life: longitudinalstudy. Br Med J 2001; 322(7292):949-53.6. Stettler N, Stallings V, Troxel AB. Weight gain inthe first week of life and overweight in adulthood.Circulation 2005; 111(15):1897-1903.7. Rao SC, Tompkins J. Growth curve for preterminfants. Early Human Dev. 2007;83:643-51.8. Gomella TL. Neonatology: Management,procedures, on call problems, disease and drugs.6th ed. New York: Mc Graw Hill – Lange;2009:47-78.9. Paul B, Saha I, DasguptaA, Chaudhuri RN.A studyon catch up growth among low birth weight infantsin an urban slum Kolkata. Indian J. Public Health.2008;52(1):16–20.10. Arifeen SE, Black RE, Caulfield LE, Antelman G,Baqui AH, Nahar Q, et al. Infant growth patternsin the slums of Dhaka in relation to birth weight,intrauterine growth retardation, and prematurity.Am J Clin Nutr 2000;72(4):1010–17.11. Ashworth A, Morris SS, Lira PIC. Postnatal growthpatterns of full-term low birth weight infants innortheast Brazil are related to socioeconomic status.J Nutr 1997;127(10):1950–6.12. Hack M, Weissman B, Bosawski-Clark E. Catch-up growth during childhood among very low-birth-weight children. Arch Pediatr Adoles Med.1996;150:1122-9.13. Gortner L, van Husen M, Thyen U, Gembruch U,Friedrich H, Landmann E. Outcome in pretermsmall for gestational age infants compared toappropriate for gestational age preterms at the ageof 2 years: a prospective study. Eur J ObstetGynecol Reprod Biol 2003;110:S93-7.14. Straus RS and Dietz WH. Effects of intrauterinegrowth retardation in premature infants on earlychildhood growth. J Pediatr 1997;130:95-102.15. Henderson G, Fahey T, McGuire W. Multi-component fortification of human breast milk forpreterm infants following hospital discharge.Cochrane Database of Systematic Reviews. 2007,Issue 4. Art. No.: CD004866. DOI: 10.1002/14651858.CD004866.pub2.16. Henderson G, Fahey T, McGuire W. Nutrient-enriched formula milk versus human breast milkfor preterm infants following hospital discharge.Cochrane Database of Systematic Reviews. 2007,Issue 4. Art. No.: CD004862. DOI: 10.1002/14651858.CD004862.pub2.17. Henderson G, Fahey T, McGuire W. Nutrient-enriched formula versus standard term formula forpreterm infants following hospital discharge.Cochrane Database of Systematic Reviews. 2007,Issue 4. Art. No.: CD004696. DOI: 10.1002/14651858.CD004696.pub3.18. De Witt SJ, Sparks JW, Swank PB, Smith K,Denson SE, Landry SH. Physical growth of lowbirth weight infants in the first year of life: impactof maternal behavior. Early Human Dev1997;47:19–34.19. Razzell P, Spence C andVines K. Poverty, birthweightand infant weight gain in Hertfordshire, 1923–1939.Int J Epidemiol 2004; 33(6):1228–33.

Prognostic factors for normal postnatal growth rate in low birth weight infants

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Prognostic factors for normal postnatal growth rate in low birth weight infants

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