Umbilical cord blood nutrients in low birth weight babies in
relation to birth weight & gestational age
K.E. Elizabeth, Viji Krishnan & T. Vijayakumar*
SAT Hospital, Government Medical College, Thiruvananthapuram & *University of Health Sciences
Kozhikode, India
Received April 10, 2007
Background & objectives: Low birth weight (LBW) babies are a vulnerable group and represent two outcomes - preterm birth (preterm LBW) and term with intrauterine growth retardation (term LBW). LBW babies are considered to have low nutrient reserve, but the extent of deficiency as compared to the normal babies and the differences between preterm LBW and term LBW are unclear. This study was carried out to look at key anthropometric, biochemical and clinical (ABC) parameters of LBW babies, both preterm and term, in comparison to a control group of term normal weight babies.
Methods: A group of 500 babies was selected at birth from a tertiary care teaching hospital and categorized into LBW (n=251) with preterm LBW (n=59), term LBW (n=192) and term controls (n=249). Two controls were dropped as tests could not be performed in the available cord blood sample. Key anthropometric and biochemical parameters were measured. Socio-economic status, age, parity, height and pre-delivery haemoglobin of the mothers were also recorded.
Results: The maternal characteristics were comparable in the three groups. Socio-economically, majority of them belonged to lower middle or upper lower class (Class III and IV) representing the non affluent. All the anthropometric measurements and nutrients measured namely total protein, albumin, cholesterol, triglycerides, calcium, magnesium, zinc and iron were significantly lower in LBW babies compared to term control babies. These values were lowest in preterm LBW followed by term LBW. Total iron binding capacity (TIBC) showed inverse association with iron. Some of the babies including control babies had protein, albumin, calcium and iron below the normal range and mean albumin, calcium and iron levels were below the normal range in all the three subsets.
Interpretation & conclusions: Preterm and term LBW babies are born with significantly lower nutrient reserves at birth compared to term control babies. Normal weight babies from the non affluent sections also have low nutrients especially albumin, calcium and iron. As these levels are liable to be further lowered by recurrent infections and inappropriate feeding habits, nutritional surveillance, extra feeding and supplements like calcium and iron are recommended for such vulnerable babies to promote optimum growth and to prevent deficiencies. This is important as currently, there are no clear or uniform recommendations for extra feeding and nutrient supplements to LBW babies and no supplements other than exclusive breast feeding are recommended for term normal birth weight babies. Extra nutritional inputs for LBW and selected non affluent babies along with care of the prospective and prenatal mothers for ensuring adequate transfer of nutrients to the offspring seem necessary. Such interventions can be integrated with the existing health care programmes to reach all the beneficiaries.
Key words Cord blood nutrients - LBW babies - preterm LBW - term LBW 128
Maternal age, parity, height and pre-delivery haemoglobin were also recorded. Institutional ethics committee clearance and informed consent from all the mothers were obtained.
Detailed clinical examination and anthropometric measurements were done in all the babies. Gestational age calculation was based on first trimester ultrasound when available and the New Ballard Score4. Anthropometric measurements were done using standardized equipments and procedures by a single investigator ensuring intra- observer reliability5. Weight was measured to the nearest 10 g using electronic scale (ATCO Weighing Solutions Co, Ltd., Mumbai, Model D 1.5 AW 15- BW, capacity 15 kg, least count 10 g with LED display) and length to the nearest 0.1 cm using infantometer supplied by Nestle India Co. Mid-arm circumference (MAC), occipito frontal circumference (OFC) and body mass index (BMI) were also recorded. Umbilical cord blood (10 ml) was collected from the placenta of all the subjects within five minutes of delivery into heparinised tubes and centrifuged for 8 min. The serum separated by centrifugation was used for analysis without delay. The source of chemicals, substrates and diagnostic kits for analysis were first identified as per standardized procedures6. The specific colorimetric assays were done based on the following principles; total protein (Biuret), Serum Albumin (Bromocresol Dye), cholesterol (CHOD-PAP), HDL cholesterol (phosphotungstate/ magnesium), triglyceride (GPO Grinder), calcium (Arsenazo III), magnesium (Xylidyl blue), zinc (4-Br PAPS) and iron (chromazurol B)6. The chemicals and solvents used were of analytical grade available from the following sources; cholesterol and triglyceride (Sigma Chemical Co., USA), protein and albumin (InVitria Human, London), calcium (Transasia Biomedical Ltd., Mumbai), magnesium (Wako Chemical GmbH, Germany), zinc (Carlo Erba, Italy), iron (Liquicolor, Stan Bio, Stan Antonio, Tex) and TIBC (Human). Colorimetric method is cheap, but not the best. It was selected as per feasibility and availability of resources. Biochemical tests were not done in the maternal blood due to limited resources. The collected data were analyzed with SPSS (Version 9.0) statistical package using t test and chi square test. The statistical significance was set at 5 per cent (P <0.05). As the data were normally distributed, transformation of the variables was not needed prior to analysis.
Worldwide, 15.5 per cent of all births, more than 20 million, are born as low birth weight (LBW) babies. More than 95 per cent of these LBW babies are born in developing countries1. India alone accounts for 40 per cent of the incidence of LBW babies in the developing world1. LBW is the key determinant of neonatal mortality, morbidity, subsequent growth and developmental retardation and also early onset of adulthood diseases1,2. However, it represents two groups, preterm LBW and term LBW. Nutritional reserve especially micronutrient stores are considered to be low in LBW babies at birth. The extent of this deficiency in preterm and term LBW babies is likely to be different. Objective data in this regard from developing countries like India are scanty. Current recommendations for nutritional and micronutrient supplementation and complementary feeding for LBW babies need to be modified based on the differences between these two groups. We undertook this study with the objective to look at key anthropometric, biochemical and clinical (ABC) parameters of a group of LBW babies at birth, both preterm and term, in comparison to a control group of term normal weight babies.
Material & Methods
This observational study was undertaken in a tertiary care teaching hospital in Kerala, India. A group of 500 babies was enrolled from 16,368 deliveries during the one year (January-December 2002) study period. The sampling technique was as follows: considering the 15 per cent prevalence of LBW in this region, out of the 16,368 newborns, 2455 babies were expected to be born as LBW in one year. Taking into account the feasibility and available resources, 10 per cent of this subset, i.e., 246 LBW babies and equal number of controls were proposed for the study. This was approximated as 250 cases and 250 controls. Random sampling was done for case selection and the next term normal baby was enrolled as the control. They were grouped as LBW (n=251) and term controls (249). There were 59 preterm LBW (<37 wk gestation and weight < 2.5 kg), 192 term LBW (>37 wk and <2.5 kg) and 249 term controls (>37 wk and >2.5 kg). Only infants from uncomplicated pregnancies were included. Babies with congenital malformations and/ or major systemic diseases evident at birth and products of multiple pregnancies like twins were excluded from the study. Socio-economic status of the family was assessed using the Kuppuswami scale3.
Table I. Maternal characteristics in the study groups (n=498) Parameters Preterm LBW Term LBW Term
(n=59) (N=192) control (n=247) SES Class I & II 13 (22.0) 29 (15.1) 63 (25.5)*
No. (%)
SES Class III & IV 46 (78.0) 163 (84.9) 184 (74.5) No. (%) Parity - Primi 34 (57.6) 122 (63.5) 133 (53.8) No. (%) Parity - Multi 25 (42.4) 70 (36.5) 114 (46.2) No. (%) Maternal 23.8 ± 3.8 23.8 ± 3.9 24.2 ± 3.9 Age -yr Mean ±SD Maternal height-cm 149.3 ±3.6 152.3 ± 4.1 153.8 ±4.1 Mean ±SD Maternal 11.0 ± 1.1 10.9 ± 0.9 11.1 ± 0.9 haemoglobin-g/dl Mean ± SD
*3 belonged to Class I in term controls & none belonged to Class V
in any subsets; SES, Socio-economic status; Class I- Upper, Class II- Upper middle, Class III- Lower middle, Class IV- Upper lower, Class V- Lower lower
Table II. Anthropometric parameters in the study groups (n=498) Parameter Preterm Term LBW Term control
LBW (n=59) (n=192) (n=247) Mean ± SD Mean ± SD Mean ± SD
(Range) (Range) (Range) Weight (kg) 1.65 ±0.40* 2.18 ±0.24* 2.82 ±0.30 (1.0-2.4) (2.1-2.4) (2.5-3.8) Body length 44.50 ±0.85* 44.87 ±0.58* 47.06 ±1.18 (cm) (43-46) (43-47) (44-50) OFC (cm) 31.21 ±0.61* 31.48 ±0.55* 32.75 ± 0.63 (30-32.5) (30-32.5) (31.5-34.5) MAC (cm) 7.34 ±0.49* 7.43 ±0.33* 9.13 ± 0.76 (6.6-7.9) (6.4-7.9) (8.7-9.6) BMI (kg/m2) 10.48 (0.92)* 10.97 ±0.91* 12.90 ±0.94 (P<0.05) (9.4-12.5) (8.4-12.3) (12.7-15.9)
*P<0.05 compared to control; OFC, occipito frontal circumference;
MAC, mid arm circumference; BMI, body mass index
Results
A group of 500 babies born during a one year period was selected for the study, 251 LBW and 249 term controls. Two controls were dropped as biochemical tests could not be performed in the available cord blood. There were 247(49.6%) term normal weight control babies and 251 (50.4%) LBW babies. The term control: term LBW: preterm LBW ratio was 5:3.8:1.2. There was no significant difference between the three groups
with respect to male: female ratio. There were no gender-related differences in any of the variables studied. There was no statistically significant difference in the maternal characteristics like socio-economic status, age, parity, height or mean pre-delivery haemoglobin level between the three groups (Table I). Socio-economically, majority belonged predominantly to lower middle and the upper lower class (Class III and IV) representing the non affluent. This was a reflection of the population making use of health care facilities in the government sector. Anaemia was not a significant condition in the mothers prior to delivery as these were booked cases on iron supplements.
All the measured anthropometric parameters were lowest in preterm LBW followed by term LBW group and the highest in term control group (P<0.05). Among the LBW babies, mean weight was < 2.4 kg, length <47 cm, OFC < 32.5 cm, MAC <8 cm and BMI was < 12.5 kg/m2. In term controls, mean weight was 2.82 kg, length 47.06 cm, OFC 32.75 cm, MAC 9.13 cm and BMI was 12.9 kg/m2 (Table II). The biochemical parameters showed the same trend and the mean values of protein, albumin, total cholesterol, triglycerides, calcium, magnesium, zinc and iron were lowest in preterm LBW followed by term LBW and highest in term controls (P<0.05). HDL cholesterol was slightly higher in LBW babies and this test could be done in first 100 cases due to technical reasons (Table III). Total iron binding capacity showed inverse association with iron level. Mean total protein was below the normal range in preterm LBW and albumin was below the normal range in all the three subsets. Similarly mean calcium and iron levels were below the normal range in all subsets including term controls; 9 per cent of the term control group had calcium level below normal as compared to 28 per cent in term LBW group and 34 per cent in preterm LBW group after correcting for hypoalbuminaemia. 12 per cent of the term control group, 24 per cent of the term LBW group and 36 per cent of the preterm LBW group had zinc level below normal range. Majority in all the three subsets had iron level below the normal range.
Discussion
LBW is a major public health problem in developing countries like India, where the incidence of LBW babies is alarmingly high to the tune of nearly 30 per cent1. Weight at birth is a good indicator not only of the mother’s health and nutritional status, but also of the
Table III. Various biochemical parameters of the study groups at birth (n=498)
Parameter with Preterm LBW (n=59) Term LBW (n=192) Term Control (n=247) normal range Mean ± SD (Range) Mean ± SD (Range) Mean ± SD (Range) Total protein (g/dl) 4.24 ±0.525*# 4.76 ±0.518* 5.50 ±0.735
(Normal range Preterm 4.3-7.6 & (2.9-5.9) (3.9-7.1) (4.4-7.4) Term 4.6-7.4 )
Albumin (g/dl) 1.82 ±0.264*# 2.131 ±0.345* # 2.494 ±0.391#
(Normal range Preterm 1.8-3.0 & (1.1-2,6) (1.6-3.4) (1.7-3.4) Term 2.5-3.4) Total cholesterol (mg/dl) 51.46 ±19.39* 59.92 ±19.81* 69.79±19.81 (Normal range 45-182) (23-111) (26-119) (29-128) Triglyceride (mg/dl) 52.10 ±18.87* 56.6 ±18.09* 66.66 ±20.30 (Normal range 10-98) (20-108) (28-140) (29-140) HDL cholesterol $ (mg/dl) 43.00 ±1.05 42.27 ±1.10 36.08 ±2.86 (Normal range 35-84) (42-43) (41-44) (31-41) Calcium (mg/dl) 5.67 ± 0.89*# 7.11 ± 0.94* # 8.08 ±0.96*# (Normal range 9-11.5) (3.5-7.9) (4.6-10.2) (5.4-10.6) Magnesium (mg/dl) 1.62 ± 0.31* 1.73 ±0.22* 1.96 ±0.19 (Normal range 1.2-2.6) (1.0-2.2) (1.0-2.2) (1.2-2.4) Zinc (µg/dl) 70.25 ±24.59* 78.09 ±18.39* 92.24 ±19.40 (Normal range 64-118) (32-119) (41-131) (38-138) Iron (µg/dl) 75.73 ±22.65*# 86.74 ±21.97*# 96.25 ±21.08# (Normal range100-250) (51-118) (51-130) (53-138) TIBC (µg/dl) 223.41 ±22.34 213.37 ±21.98 203.47±21.72* (Normal range NB-60-175) (172-259) (169-249) (136-247)
*P<0.05 compared to term control; #Below the normal range; $Done only in first 100 cases (preterm LBW-25, term LBW-25 & term
controls-50) TIBC, total iron binding capacity
outcome for survival, growth, long-term health and psychosocial development of the baby7,8. LBW babies weighing less than 2.5 kg, face a greatly increased risk of dying and is the main contributor with respect to neonatal, infant and under five mortality. Those who survive have impaired immune function and have increased risk of early onset of adulthood diseases like diabetes and heart disease later in life, as per the ‘Barker hypothesis’9 and the ‘fetal origin of adulthood disease (FOAD) hypothesis2. They are also likely to remain malnourished and may have lower IQ and cognitive disabilities leading to school failure and learning difficulties7,8. There is also growing evidence that those adults born with LBW suffer an increased risk of coronary artery disease (CAD) and non insulin dependent diabetes mellitus (NIDDM), high blood pressure, obstructive lung disease, high blood cholesterol and renal damage9,10. As the lowered nutrient levels at birth are liable to be further lowered by recurrent infections and inappropriate feeding habits, they need nutritional surveillance, extra feeding and supplements. If optimum catch up growth is not
achieved by at least two years of age, these children will add to the pool of malnutrition. Growth faltering and developmental delay is the rule in those who continue to be malnourished11. Very low levels of micronutrients have been documented in children with malnutrition12 and positive outcome in growth has been documented using comprehensive early interventions including nutritional and developmental inputs12,13 and micronutrient supplements, especially zinc14.
MAC and BMI are now identified as two important anthropometric parameters in the newborns as well. Mean MAC >9cm and BMI around 13 kg/m2 noted in term control babies observed in this study is comparable to our earlier study15. MAC can be used as a simple tool to pick up LBW babies when accurate weighing is not possible. Tracking of BMI from birth to adulthood is considered as an intervention by itself to ensure optimum weight for height, to prevent both undernutrition and obesity.
Foetal homeostasis of calcium, magnesium, iron and zinc is thought to be partly independent of maternal
factors, with a preferential concentration towards the foetus in most instances and both the placenta and mammary gland exert activating, inhibiting or gradient mode of action for selected trace elements16,17. Zinc and iron levels have been shown to be higher in cord blood as compared to maternal blood, but copper has been found to be lower than maternal blood18,19. However, iron transfer has been documented to be affected proportionately to the degree of maternal hypoferriemia20.
The present study showed lowest values for the all the nutrients tested in preterm LBW followed by term LBW group as compared to the control group. Medical complications of preterm birth together with immaturity of digestion, absorption and metabolism will lead to poor intake and assimilation of nutrients. The stress of hypoxia and infection while in the neonatal units deplete the already limited stores of nutrients. Some preterm and term LBW infants have ongoing medical problems such as chronic lung disease, which increase nutrient requirements and chewing and swallowing difficulties which decrease nutrient intakes. It is known that preterm infants have special nutritional needs in the period post-discharge from the neonatal unit21.
Calcium plays a vital role in bone and teeth formation, neuromuscular function and hemostasis. Jitteriness, tetany and seizures can occur with low levels and this is a medical emergency in sick and LBW babies. The observation that low calcium level can occur even in term control babies endorses the practice of giving calcium to babies with medical problems like birth asphyxia22. Sub-clinical magnesium deficiency has been implicated in the development of insulin dependent diabetes mellitus, hypertension and attention deficit hyperactivity disorder (ADHD)23-25. The significantly lower magnesium levels found in LBW group could also be a putative link with foetal programming26. Zinc is a component of a large number of metalloenzymes and there is a high concentration of zinc in the brain. The consequences of zinc deficiency are several with severe impact on human health. These include growth retardation, male hypogonadism, neurosensory changes, abnormal dark adaptation and changes in taste acuity, delayed wound healing, abnormal immune functions, and impaired cognitive functions27. Beyond the neonatal period, iron is required for functioning of neurotransmitter system by production of dopamine, serotonin and GABA. The consequence of iron deficiency is now believed to be irreversible, decreasing physical stamina, cognitive ability and learning ability28,29.
Low serum protein and albumin among newborns is of concern as it will lead to reduced oncotic pressure and carrier proteins. The serum lipid profile in LBW babies has come under scrutiny as a potential risk factor for hypercholesterolaemia in adult life30. Our study showed decreased cholesterol and triglyceride levels in the cord blood of LBW babies. A recent meta analysis showed that impaired foetal growth does not have effects on blood cholesterol levels that would have a material impact on vascular disease risk31.
In conclusion, preterm and term LBW babies are born with significantly lower nutrient reserves at birth compared to term control babies. Some normal weight babies from the non affluent sections are also born with low nutrients especially albumin, calcium and iron. These levels are liable to be further lowered by recurrent infections and inappropriate feeding habits. Current recommendations for infant feeding practices in India do not take into account the specific needs of preterm LBW, term LBW and term normal weight infants belonging to the non affluent sections. There is a need for nutrient supplements to all LBW babies and perhaps calcium and iron to all babies belonging to the non affluent. Such supplementation may also be needed for the pregnant women to ensure optimum growth and better nutrient transfer to the offspring. These interventions can be integrated with the existing health care programmes to reach all beneficiaries.
Acknowledgment
Authors acknowledge the Kerala State Council for Science Technology and Environment for financial support.
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