Effect of Birth Weight, Gestational Age, Sex and Intrauterine Growth on Mortality and Morbidity Profile of very Low Birth Weight Babies (VLBW)

Introduction: Very Low birth weight is associated with serious neonatal morbidity. Biologic factors are major determinants in their outcome. We analysed the effect of birth-weight, gestation, sex and intrauterine growth in the mortality and morbidity profile of VLBW babies during the neonatal period. Methodology: This is a cross sectional retrospective observational study from April-2012 to August-2014. Baseline demographics, disease features of 97 VLBW babies were analyzed. Results: Survival at discharge was 91.75%. There was significant difference in need of ventilation, surfactant, Apnea, ROP, IVH >/= Grade-II, Culture-negative Sepsis among all gestational subgroups. Survival increased as gestation advanced. Maximum decrease in mortality has occurred beyond 28 weeks. Maximum odds difference in need of ventilation, BPD was noted around 28 weeks. Major difference in HS-PDA, IVH, NEC were noted around 30 weeks. Significant difference in need of surfactant, apnea and anemia was observed around 32 weeks. Major decrease in HMD, Hyperbirubinemia and sepsis were identified around 34 weeks. Analysing intrauterine growth, Significant difference in Need of ventilation, surfactant use, IVH, NEC, Anemia and death was noted between AGA and SGA. Analysing birth weight wise, Survival improved as birth-weight increased. There was significant difference in HS-PDA and IVH in all birth-weight subgroups. Maximum decrease in death was noted in babies >1000g. Maximum odds difference in BPD, Apnea, Hyperbilirubinemia, IVH, Anemia, ROP and culture negative sepsis occured around 800g. Major difference in HMD, NEC, Culture positive sepsis was observed around 1000g. Significant odds difference in HS-PDA occurred around 1200g. Maximum decrease in need of surfactant and ventilation was noted around 1400g. Conclusion: There was no difference between male and female in survival or morbidities. Survival improved with advancing Gestation, Intrauterine growth and Birth-weight. Analysing intrauterine growth, Significant difference in Need of ventilation, surfactant, IVH, NEC, Anemia and death was noted between AGA and SGA. Significant variations in morbidity profile were noted among birth weight and gestational age subgroups.


Introduction
The very low birth weight babies are at risk from a wide range of hazards resulting from immaturity of structure and function of various organs [1]. With advanced perinatal & neonatal care, survival of VLBW infants has increased globally. Well equipped, experienced NICUs also have contributed to the increasing survival of VLBW neonates [2,3,4,5]. Studies have reported normal outcomes in 73% of these babies figures vary widely from country to country with reports of up to 90% survival from developed countries to 40% in the developing world [6]. According to 2010 National Vital Statistics Report, in 2006 the mortality rate among infants with VLBW was  [7]. There is paucity of data regarding outcome of VLBW babies based on gestational age, birth weight applicable to our population. Outcomes in VLBW infants are best understood as an interaction between biological vulnerability & environmental factors. Does biological factors (birth weight, gestational age, sex, intrauterine growth) has a significant impact on survival and morbidity profile during neonatal period is our research question.

Primary Outcome:
To determine the effect of gestational age, birth weight, sex and intrauterine growth in the mortality and morbidity profile of very low birth weight babies during the neonatal period.
Methodology: T his cross-sectional retrospective study was performed from April 2012 to August 2014 on all hospitalized VLBW babies. Relevant pre and perinatal data upto the time of discharge or death , including complications during the course of hospitalization, were collected from the case notes, documented on a predesigned proforma with preformed diagnostic criteria and analysed. The gestational ages were determined by obstetric assessment and modified Ballards score, when antenatal reports were not available [8]. Hyaline membrane disease was diagnosed according to clinical and radiological findings. Retinopathy of prematurity was diagnosed by an ophthalmologist and classified in grades 1 to 5 according to international classification [9]. BPD was diagnosed according to the criteria of Bancalari et al [10] including clinical and radiographic features together with the requirement of oxygen therapy at 28 days of age. Bronchopulmonary dysplasia (BPD) was defined by oxygen requirements at 28 days of life and chronic radiographic changes [11]. The diagnosis of sepsis was confirmed by isolation of the organism in the blood. Patent ductus arteriosus was diagnosed clinically and confirmed by echocardiography. The diagnosis of Intraventricular Hemorrhage was made by ultrasonogram and was classified according to Papile and Bursten [12]. NEC was determined by the clinical and radiological criteria of Bell et al [13] and only definite NEC (Bell stages II-III) was included. Growth was plotted in Fenton growth charts. Interventions: Preterm care as per standard unit protocol. Data Analysis: Detailed information including gestational age at diagnosis, birth weight were collected from hospital records of all VLBW admissions. Outcomes were classified as neonatal survival or death. Categorical variables were analyzed using Chisquare analysis with Yates correction. Student't' test was used to compare the means. A p-value of <0.05 was considered significant.

Results
There were total 1191 newborn admissions during the study period. Among these 1191 babies, 97 babies (8.14%) were very low birth weight babies and were included in the study. Survival rate at discharge among VLBW babies was 91.75%. Among VLBW babies 55.67% (n=54) were male & 44.32% (n=43) were female. However there was no statistical significance (2-Tailed probability=0.2633).

Effect of Gestational Age on Mortality & Morbidity Profile of VLBW Babies
Analysing the gestational subgroups, we estimated the morbidity and mortality between the subgroups.  Table 1 shows the distribution of morbidity profile based upon the gestational subgroups.

Table1: Distribution of Morbidity Profile-Gestation Wise-Subgroup Analysis
A one-sample t-test between proportions was performed to determine whether there was a significant difference among morbidities and death based on gestational age subgroups. The t-statistic was analysed and p value<0.05 was considered significant. Gestation wise < 28 & >28weeks; <30 & >30 weeks; <32 & >32 weeks; <34 & >34 weeks were analysed. It is well known that immature infants (particularly those born <32weeks ) are at higher risk for mortality and morbidity and failure to consider gestational age leads to major problem in interpretation that hinder decision-making at both clinical and public health levels [17]. There was significant difference in need of ventilation and surfactant use, Apnea, ROP, (IVH) >/= Grade II, Culture negative Sepsis in all subgroups. However culture positive was more significant between <28 & >28weeks. Significant difference in Jaundice was noted between <34 & > 34weeks. Significant difference in HMD was noted between < 32& >32weeks and <34 & >34weeks. BPD and anemia requiring PRBC transfusion, was significant in all subgroups except <30 & >30 weeks. Hemodynamically significant Patent Ductus Arteriosus (HS-PDA) requiring treatment, was significant in all subgroups except <32 & >32weeks. NEC was significant between < 28 & >28weeks and <34 & > 34weeks. Statistical significant difference in death was noted in all subgroups. Survival increased significantly as gestation advanced.   Table 2 depicts the comparison of proportions based upon gestational subgroups.
Analysing the proportions of morbidities and mortality among each gestational subgroup, we compared the ratio of morbidities and mortality in each subgroup to 1. estimate maximum risk difference of morbidity and mortality 2. to analyse the gestational age when 0 mortality and 0 individual morbidity was attained.     Table 3 shows the sex wise comparison of morbidity profile of VLBW babies. There was no Statistical significant difference in death and morbidities between male and female subgroups.   Table 4 shows the intrauterine growth wise comparison of morbidity profile of VLBW babies.

Effect of Intrauterine Growth in Mortality & Morbidity Profile of VLBW Babies
There was significant difference in Need of ventilation, surfactant use, IVH, NEC, Anemia and death was noted between AGA and SGA.

Effect of Birth Weight in Mortality & Morbidity Profile of VLBW Babies
Analysing the Birth Weight subgroups, we estimated the morbidity and mortality between the subgroups. We analysed the variation of mortality and morbidity among,

Discussion
Survival rate at discharge among VLBW babies in our study was 91.75%. There has been global improvement in VLBW survival. The American Academy of Pediatrics policy statement on neonatal care states that only Level III hospitals should take care for infants less than 32 weeks gestation [14]. Since 1990, Healthy People Objective for 2000, 2010 and 2020 have included the goal to increase the proportion of VLBW infants born at LEVEL III hospitals to 90 percent [15]. In 2008 the National Quality Forum endorsed a series of 17 quality measures for perinatal care. One of these quality measures states that infants <1500g should be delivered at a hospital with a Neonatal Intensive care unit [16]. Though majority of our VLBW babies were out born, we noted good survival due to prompt early referral and golden hour management including temperature. There was significant difference in need of ventilation, surfactant, Apnea, ROP, IVH >/= Grade-II, Culture-negative Sepsis among all gestational subgroups in our study. Survival increased as gestation advanced. Maximum decrease in mortality occured beyond 28 weeks. Maximum odds difference in need of ventilation, BPD was noted around 28weeks. Major difference in HS-PDA, IVH, NEC occured around 30 weeks. Significant difference in need of surfactant, apnea, anemia was observed around 32weeks. Major decrease in HMD, Hyperbirubinemia,and sepsis occured around 34weeks.
J C Velaphi et al in his study found that female gender had lesser morbidity than male. Similar findings were also noted by Cartlidge et al and Stevenson DK et al [18,19,20]. However we did not observe the male disadvantage in our study. Birth weight in particular is strongly associated with fetal, neonatal and postneonatal mortality and with infant and child morbidity [21,22]. Impairments in fetal growth can have adverse consequences in terms of mortality, morbidity, growth and performance [21,22,23]  There were no differences in odds of survival for infants in the 1100-1199g and 1000-1099g weight groups [18].We noted Statistical significant difference in death was noted in all subgroups. Survival increased significantly as birth weight increased.

Conclusion
With advances in neonatal care particularly with VLBW and premature babies there is improvement in survival with decreasing morbidities. There was no difference between male and female in survival or morbidities. We noted improved survival with advancing Gestation, Intrauterine growth and Birth weight. Analysing intrauterine growth, significant difference in Need of ventilation, surfactant, IVH, NEC, Anemia and death was noted between AGA and SGA. Significant variations in morbidity profile were noted among different birth weight and gestational age subgroups. The present study is limited because the study population is small and the study period is short. However, a good initial database is presented and can be useful for future research in this region. If substantiated by future prospective studies, these data may help clinicians to counsel families regarding the adverse morbidity and mortality based on gestation, sex, intrauterine growth and birth weight.