Analysis Of Early Postnatal Growth Level And Pattern Of Preterm Infants And Their Associated Perinatal Factors

BackgroundWith the continuous development of obstetric and neonatal intensive care technology,more and more preterm infants are able to survive.Since early infancy is a period of significant increase in cell number and size,growth disorders that occur in preterm infants at this time can cause permanent adverse effects,such as short stature and increased risk of metabolic disease in adulthood.Preterm infants are high-risk populations with poor growth and require close monitoring and follow-up in order to take timely interventions to improve their growth.Standard growth data is available for healthy full-term born children,such as WHO growth standards,but growth data for preterm infants during hospitalization and after discharge are both limited,and the growth curve of which is not satisfactory to record the optimal postnatal growth of preterm infants.There is still no consensus regarding the most suitable growth charts to monitor and evaluate postnatal growth of preterm infants.Two common ways for assessing the growth of preterm infants are:1)before corrected term age,the intrauterine fetal size standard or the birth size standard for live births are used,after corrected term age,growth charts constructed from growth data of term infants are used;2)assessing the postnatal growth of preterm infants after birth based on longitudinal growth data of preterm infants with normal fetal growth and almost no short-term complications,such as the newly published INTERGROWTH-21st International Preterm Postnatal Growth Standard.The former is widely used at present,but increasing evidences have concluded the inappropriateness to evaluate postnatal growth with intrauterine growth reference,which may lead to inadequate growth of preterm infants,and it has also been controversial to use growth data of term infants to assess the growth of preterm infants after discharge since they have very different perinatal environments.The latter in theory could better reflect the actual postnatal growth level and pattern of preterm infants and monitor abnormal growth.However,longitudinal growth data are still of great heterogeneity attributed to conceptual and methodological differences among different studies and thus not necessarily suitable for assessing all preterm infants.The current longitudinal growth data for preterm infants are limited and do not reflect long-term outcomes.In China,their suitability for monitoring the postnatal growth of preterm infants has not been verified.In addition,preterm infants can be stratified by some important perinatal indicators and be divided into different subgroups.For example,early preterm,moderate preterm,and late preterm infants according to gestational age(GA);twin preterm and singleton preterm infants according to the number of fetus;normal birth weight(NBW),low birth weight(LBW),very low birth weight(VLBW),and extremely low birth weight(ELBW)preterm infants according to birth weight(BW);small for gestational age(SGA),appropriate for gestational age(AGA)and large for gestational age(LGA)according to BW and GA,etc.There is no clear conclusion as to whether there are differences in the growth levels and patterns of different subgroups of preterm infants.Follow-up and monitoring of preterm infants is of great importance for comparison of growth patterns among different subgroups of preterm infants.The appropriate growth targets and assessment methods for different subgroups of preterm infants are urgently needed for determination in clinical practice.This study was a longitudinal follow-up study of growth and development of preterm infants conducted in Shandong Provincial Qianfoshan Hospital.All subjects were sampled from a data set of 795 preterm infants born between January 2014 and April 2017 in obstetrical department and registered in Child Health Care Center.The postnatal growth between birth and corrected age of about 2 years old(PMA 156 weeks)was systematically monitored,and detailed research and analysis were carried out in three parts:1)Postnatal length and weight growth velocities and their associated perinatal factors in healthy late preterm infants from birth to term-corrected age;2)Comparison of postnatal growth level and pattern of singleton preterm infants with singleton term infants and commonly-used or recommended growth references/standards in the first two years of life;and 3)Comparison of postnatal growth level and pattern of twin preterm infants with singleton preterm infants and commonly-used or recommended growth references/standards in the first two years of life.Our overreaching goal was to provide evidences of growth patterns of current preterm infants stratified by different perinatal factors,to analyze the appropriateness of commonly-used international growth charts in the growth assessment of local preterm infants,and to explore the need to construct specific growth curve of local preterm infants with different perinatal characteristics.CHAPTER I.Postnatal length and weight growth velocities and their associated perinatal factors in healthy late preterm infants from birth to term-corrected ageObjectivesLate preterm infants are defined as infants born at 34-0/7 to 36-6/7 weeks of postmenstrual age(PMA).They consist the largest proportion of preterm infants and 8-9%of total births.Nowadays,neonatal services do not routinely follow-up all late preterm infants because to do so would require significant resources.However,late premature birth still interrupts normal in utero fetal development during the last 6 weeks of gestation which is considered as a time-sensitive,irreversible decision point in growth and development.There are accumulating evidences for higher risks of early and later health consequences in late preterm infants,which would translate into significant medical,emotional,and economic impacts at the population level.However,the postnatal growth of late preterm infants has not attracted widespread attention.In this part we aimed to monitor and evaluate the postnatal length and weight growth velocities and their associated perinatal factors in healthy late preterm infants without restriction of neonatal complications and nutritional problems.Subjects and Methods1.Subjects:As part of ongoing longitudinal follow-up study of growth and development of preterm infants in Shandong Provincial Qianfoshan Hospital in China,599 healthy late preterm infants without neonatal complications and nutritional problems were sampled from 795 preterm infants born between January 2014 and April 2017.2.Methods:Perinatal factors,growth parameters,growth velocities(ΔHAZ andΔWAZ:Z-score changes of length and weight)from birth to term-corrected age were documented.Associated variables of growth velocities were analyzed by bivariate and multivariate regression analyses.Adjusted ΔHAZ and AWAZ were compared between/among subgroups of associated variables using analysis of covariance.Catch-up growth were defined as ΔHAZ or ΔWAZ>0.67.P<0.05 was defined as statistical significance.Results1.From birth(mean PMA 35.38 weeks)to corrected-term(mean PMA 40.84 week),the length and weight increment was 5.58±2.05 cm and 1.41 ±0.43 kg,respectively.2.According to Fenton reference,the mean ΔHAZ and AWAZ were 0.28,0.65,respectively.Catch-up growth of length and weight was ubiquitous(30.7%and 46.2%,respectively).3.Larger Δ HAZ was associated with male,larger PMA at birth,younger mother and larger PMA at visit;Larger Δ WAZ was associated with male,unfavorable intrauterine growth status defined by birth weight percentile(SGA(<P10),AGA(P10-90),LGA(>P90)),twin and larger PMA at visit.4.When adjusted for associated co-variables,weight catch-up growth existed in subgroups of 36 weeks PMA at birth,male,twin and SGA,while AGA almost reached this standard with mean adjusted ΔWAZ as 0.66.Although none of these subgroups got length catch-up growth standard,infants of 36 weeks PMA at birth had statistically rapider length growth velocity than 34 and 35 weeks PMA at birth subgroups(mean adjusted AHAZs of 34,35 and 36 weeks subgroups:0.10,0.22,0.38,respectively,P<0.05).Conclusions1.Postnatal length and weight growth velocities of healthy late preterm infants from birth to termcorrected age were much superior to that of Fenton reference,especially for weight,with ubiquitous catch-up growth.2.Different associated factors for length and weight growth signified the necessity of constructing more detailed growth standards by specific stratification for associated factors.CHAPTER Ⅱ.Comparison of postnatal growth level and pattern of singleton preterm infants with singleton term infants and commonly-used growth charts in the first two years of lifeObjectivesGrowth impairment during early postnatal life has permanent detrimental effects in later life.Thus,a full understanding of optimal postnatal growth is of critical importance for improving survival and long-term outcomes in preterm infants.This requires robust growth charts to monitor and assess whether a preterm infant has potentially abnormal growth that might be indicative of adverse health conditions.Till now,the selection of growth charts is still controversial given the lack of consensus regarding the most suitable charts to use.The most prominent of these growth charts are the WHO Growth Standards and the WHO advises that these are suitable for infants from all ethnic backgrounds.However,there has always been some concern within the scientific community that certain populations or sub-populations may not be suited for applying these universal standards and that doing so may cause misdiagnosis of poor or excessive growth,especially for preterm infants.Nowadays in China,the most commonly used growth charts for preterm infants are Fenton Reference before corrected-term and WHO Growth Standards or Chinese National Growth Survey data after corrected-term,respectively.The lately published INTERGROWTH-21st International Preterm Postnatal Growth Standards,which is recommended for the assessment of preterm infants until postmenstrual age(PMA)64 weeks,has not been widely used and convinced to be suitable for monitoring postnatal growth of Chinese preterm infants yet.In order to clarify whether these commonly-used or recommended growth charts could adequately and appropriately evaluate postnatal growth of local singleton preterm infants before corrected two years old,in this study,we compared the postnatal growth of a specific population of singleton preterm infants in Jinan City in China with with their term counterparts and commonly-used or recommended growth charts(Fenton Reference,INTERGROWTH-21st Standards,WHO Growth Standards(2006)and Chinese National Growth Survey(2005)).Subjects and Methods1.Subjects:As part of ongoing longitudinal follow-up study of growth and development of preterm infants,301 eligible singleton preterm infants(mean birth PMA 34.55 weeks)and 1753 singleton term infants(mean birth PMA 40.00 weeks,as a control group)were sampled from 795 preterm infants and 2012 term infants born between January 2014 and April 2017 in Shandong Provincial Qianfoshan Hospital in China(exclusion of twins,infants with congenital malformations/syndromes and infants with less than three times of growth assessments),respectively.2.Methods:The postnatal growth from birth to PMA 156 weeks was monitored for singleton preterm and term infants.Anthropometric measurements(Weight,Length/Height,Head Circumference(HC)and Body Mass Index(BMI))and their Z-scores calculated through Fenton Reference,INTERGROWTH-21st International Newborn Size Standards and Pretenn Postnatal Growth Standards,and WHO Growth Standards were documented and retrospectively assigned into 11 age clusters from birth to PMA 156 weeks.Growth levels and/or trajectories were compared among preterm,term infants,Fenton Reference,INTERGROWTH-21st Standards,WHO Growth Standards and Chinese National Growth Survey through T test or Covariance analysis.P<0.05 was defined as statistical significance.Results1.From PMA 40 to 52 weeks,the Length,Weight,HC and BMI of singleton preterm infants was higher than singleton term infants(all anthropometric indicators for preterm and term infants had statistical significance expect for HC at PMA 40-46 weeks).From PMA 52 to 156 weeks,the postnatal growth level and pattern of singleton preterm infants was highly consistent with that of term counterparts(all anthropometric indicators for preterm and term infants had no statistical significance).2.The postnatal growth level of singleton preterm infants was obviously higher than commonly-used or recommended growth charts from birth to PMA 156 weeks(Z-scores all obviously>0).3.When singleton preterm infants were evaluated by commonly-used growth charts,the proportions of positive deviation(Z-scores>2)for all anthropometric indicators were obviously higher than the due proportion(2.3%),while the proportions of negative deviation(Z-scores<-2)were the opposite.ConclusionsThe elevated early postnatal growth level of Chinese singleton preterm infants than commonly-used growth charts and the consistent growth trajectories between singleton preterm and term infants demonstrated the possible geographical and ethnical difference and signify the necessity of construction and use of local growth reference for singleton preterm infants.CHAPTER Ⅲ.Comparison of postnatal growth level and pattern of twin preterm infants with singleton preterm infants and commonly-used growth charts in the first two years of lifeObjectivesOver the past decades,multiple pregnancies have increased dramatically around the world due to increasing maternal age at child birth and the widespread use of assisted reproductive technology.Of these,twin births account for the vast majority of multiple births and is associated with higher rates of almost all neonatal complications.The most common complication of twin pregnancies is premature birth,which leads to a significant increase in perinatal mortality and short-and long-term morbidity due to complications associated with immaturity.The proportion of twins in all preterm births is 17%,and the chance of twin pregnancies having premature birth is as high as 57%.Growth patterns of twin fetuses have been reported in many literatures.Twin fetuses without complications grow more slowly after 28 to 30 weeks of pregnancy than singleton fetuses.The combined effect of slower growth velocity of fetus in the third trimester and shortened gestational age(especially premature birth)leads to the commonly-known cognition that twin newborn infants have smaller sizes than singleton counterparts.Among twin infants and preterm infants,the twin preterm infants belong to an important cross-section,but they are often overlooked,and few studies have been studied specificly on their postnatal growth levels and patterns.Nowadays,most growth charts are constructed from growth data of singleton term-born infants,such as WHO Growth Standards,even the latest INTERGROWTH-21st Preterm Postnatal Growth Standards are based on longitudinal growth data of singleton preterm infants.However,till now,there is no concensus as whether these growth charts are suitable for assessing the postnatal growth and detecting abnormal growth of twin preterm infants.There is also little literature on the comparison of postnatal growth of twin preterm and singleton preterm infants.This part of the study was aimed to monitor and evaluate the postnatal growth level and pattern of twin preterm infants in the first two years of life,which was in comparison with singleton preterm counterparts and commonly-used/recommended growth charts.It would provide evidences of specific growth patterns of twin preterm infants and explore the necessity for construction of specific growth curves of local twin preterm infants.Subjects and Methods1.Subjects:As part of ongoing longitudinal follow-up study of growth and development of preterm infants,112 eligible twin preterm infants(56 pairs,mean birth PMA 35.07 weeks)and 301 singleton preterm infants(mean birth PMA 34.55 weeks,as a control group)were sampled from 795 preterm infants born between January 2014 and April 2017 in Shandong Provincial Qianfoshan Hospital(exclusion of infants with congenital malformations/syndromes and infants with less than three times of growth assessments),respectively.2.Methods:The postnatal growth from birth to PMA 156 weeks was monitored for twin preterm and singleton preterm infants.Anthropometric measurements(Length/Height,Weight,HC and BMI)and their Z-scores calculated through Fenton Reference,INTERGROWTH-21st International Newborn Size Standards and Preterm Postnatal Growth Standards,and WHO Growth Standards were documented and retrospectively assigned into 11 age clusters.Growth parameters of twin and singleton preterm infants in each age cluster were compared through T test or covariate analysis.Results1.At birth,after adjusted for the discrepancy of PMA at birth by covariate analysis,twin preterm boys had smaller weight and length than singletons;during PMA 40-156 weeks,there were no statistical differences between twin preterm boys and singleton preterm boys in comparison of mean PMA and all the anthropometric indicators(Length/Height,Weight,HC and BMI)(P>0.05);there were no differences in mean PMAs in twin preterm and singleton preterm girls in all the age groups,the HC in twin preterm girls was larger than that of singleton preterm girls,and there were statistical differences in most age groups(i.e.PMA 40-46 weeks,58-64 weeks,64-72 weeks,84-96 weeks,112-132 weeks.132-156 weeks,P all<0.05),the remaining anthropometric indicators(Length/Height,Weight and BMI)were of no statistical differences between twin preterm girls and singleton preterm girls in all the age groups(P>0.05).2.Compared with commonly-used growth charts,HAZ and WAZ of twin preterm infants at birth were smaller than singleton preterm infants even though the mean PMA at birth of twins was larger than singletons:1)According to Fenton reference,HAZ was-0.02(0.76)and 0.40(1.00);WAZ was-0.28(0.73)and 0.04(1.04)for twins and singletons,respectively,P<0.05).2)According to INTERGROWTH-21st Newborn Size Standards,HAZ was 0.26(1.00)and 0.74(1.19),P<0.05;WAZ was 0.03(0.79)and 0.35(1.09)for twins and singletons,respectively,P<0.05).Overall,from PMA 40 to 156 weeks,the growth levels of twin and singleton preterm infants were higher than the commonly-used international references/standards(HAZ,WAZ,HCZ and BAZ>0).Conclusions1.Twin preterm infants had smaller birth size than singleton preterm infants,but this difference disappeared since PMA 40 weeks except for HC;from PMA 40 to 156 weeks,twin preterm infants had similar growth trajectories in Length/Height,Weight,HC and BMI except that twin preterm girls had larger HC than singleton preterm girls.2.Twin preterm infants had higher growth levels than commonly-used international growth charts during PMA 40 and 156 weeks since the Z-scores calculated through these charts were all above zero.