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Rasoul-Zadeh Youldouz, Klimashkin Aleksey, Tashkent Pediatric Medical Institute, Uzbekistan E-mail: y_ras@mail.ru; aleks.klimashkin@mail.ru
RISKS OF SMALL FOR GESTATIONAL AGE BABIES: STUDY IN UZBEKISTAN
Abstract. Intrauterine growth restriction (IUGR) is an important cause of fetal, perinatal and neonatal morbidity and mortality. Neonates with IUGR experience acute problems in the perinatal and early neonatal period that can be life-threatening. The identification and description of maternal and newborn risk factors associated with an increased risk for SGA in a particular country is of obvious interest. The aim of this paper is to quantify and to describe risk factors of small for gestational age birth in Uzbekistan as one of developing countries.
Keywords: small for gestational age, risk factors, cohort study.
Background
Intrauterine growth restriction (IUGR) is an important
cause of fetal, perinatal and neonatal morbidity and mortality. Neonates with IUGR experience acute problems in the perinatal and early neonatal period that can be life-threatening. Small for gestational age (SGA) is considered as an indicator of intrauterine growth restriction, and has been associated with neonatal mortality and morbidities as well as with maj or medical problems across the life course. Long term follow up studies have shown that IUGR babies are more likely to develop coronary artery disease, hypertension and diabetes [2; 9], the so-called insulin-resistance syndrome or syndrome X [7].
World over, IUGR is observed in about 24% of newborns; approximately 30 million infants suffer from IUGR every year [3; 10]. The incidence of IUGR is six times higher in underdeveloped/developing countries when compared to that in developed countries, and this incidence can be further high in lower- and middle-income countries, as many infants are born in home with no birth records. The burden of IUGR is concentrated mainly in Asia which accounts for nearly 75% of all affected infants [5].
Multiple maternal and newborn characteristics have been identified as risk factors for SGA and it is well known that they vary between different populations. Risk factors may be related to population variations in nutrition, education, family income, smoking habits, drug use, domestic violence, marital status, age and race [4]. Therefore, the identification and description of maternal and newborn risk factors associated with an increased risk for SGA in a particular country is of obvious interest.
The aim of this paper is to quantify and to describe risk factors of small for gestational age birth in Uzbekistan as one of developing countries.
Patients and methods
We performed historical cohort study involved 3793 singleton birth that have taken place between 2010 and September 2014 in Tashkent.
We excluded cases with multiple pregnancies (n = 23), congenital malformations (n = 12), cases with birth weight less than 500 g, (n = 46) and low quality medical records (n = 190). At final analysis we had 3522 cases. Thereafter, we stratified the population by gestational age into preterm (< 37 gestational weeks), term (> 37 and < 42 gestational weeks) and post-term babies (> 42 gestational weeks). Small for gestational age babies were defined if they had birth-weight was less 10th percentile. In the frame of our study we select maternal and fetal factors that commonly associated with low birthweight.
All variables were analyzed by Student's t-test. Association between studied factors and outcomes of interest were assessed by calculation of odds ratios (ORs) and 95% CIs. Statistical significance was assumed at P < 0.05. Statistical analyses were performed using STATA V.14.0 (College Station, StataCorp LP, Texas, USA).
Results
Studied risk factors and SGA rate according to gestational age strata are presented in Table 1. SGA babies were more likely were born among preterm (14.96%), than among term (9.64%) and posterm categories (10.99%). Interestingly, preterm girls were slightly more likely to be SGA than posterm girls. Meantime male newborns were by 94,7 g heavier than female newborns (p < 0.000), and after correction for gestational age this difference increased to 102.86 g (p < 0.000).
Being first born was associated with higher risk of SGA regardless newborn's gender. First- and second-born SGA rates were 14.3% and 10.1%, respectively; compared with the firstborn, the second-born had a lower risk of being SGA (OR = 0.71).
Short inter-pregnancy intervals (less than 1 year) in comparison to inter-pregnancy intervals of 1-2 years, were followed more often by preterm birth (11.1% versus 6.3%; OR - 1.86; 95% CI 0.86-4.04) and small for gestational age babies (15.79% versus 14.08%; OR1,14; 95% CI 0.38-0.43).
The rate of preterm and small for gestational age babies among group of women younger 25 years of age with inter-pregnancy intervals less than 1 year was 14.81%. In comparison, in referral group involved women aged 25-29 years and interpregnancy interval of1-2 years, these figure was 15.52%. In category of oldest pregnant women (more than 35 years) with short interpregnancy intervals the rate of preterm and small for gestational age babies was registered at the level of 22.22%.
Additionally we found, that hypertension (all types of hypertensive disorders in pregnancy) delivery of low birth-weight baby was more likely in the case of preterm than pos-term pregnancy.
Vast majority of women in cohort were married or living in civil marriage (n = 3073). Among no-married (i.e. divorced/widowed, single) probability of giving birth SGA baby was higher and absolute percentage difference was 2.01 for divorced/widowed and 2.19 for single women. Odds ratios
Table 1. - Studied risk fac
for these categories was - 1.24 (95% CI = 0.79-1.92) and 1.26 (95% CI = 0.84-1.89) respectively.
Among women with SGA firstborns, 28% had recurrent SGA infants. This recurrent SGA group made up 4% of all second births and contributed to 40% of all SGA second births.
Rate of SGA was not significantly differ from male and female newborns. Meanwhile, subsequent deliveries were associated with decreased risk of birthweight deficit. Compared to siblings born later, firstborns were more likely develop birthweigh deficit in the case of term or posterm deliveries. SGA rate was higher if interpregnancy intervals were less than 1 year, and this was irrespective of gestational age at delivery. Women with history of low weight births had high risk of reccurence SGA babies, and this was either irrespective of gestational age at delivery. The study also found that risk of SGA is higher in women older 35 and younger 25 years as well as smokers, passive smokers and women who were not in family relations.
's and SGA rate in cohort
General N = 3522 Preterm N = 177 Term N = 3154 PostermN = 191
SGA / gen \ (n = 351; 9.96%) SGA f pret (n = 26; 14.69%) SGA term (n = 304; 9.64%) SGA f post (n = 21; 10.99%)
1 2 3 4 5
Gender
Male 1863(8.48) 90(14.44) 1676 (8.17) 97 (8.25)
Female 1659 (11.63) 87 (14.94) 1478 (11.30) 94 (13.83)
Birth order
First 1390 (11.58) 59 (15.25) 1244 (11.33) 87 (12.64)
Second 1129 (8.41) 69 (10.14) 1009 (8.33) 51 (7.84)
Third and more 1003 (9.47) 49 (20.41) 901 (8.77) 53 (11.32)
Interpregnancy interval (years)
<1 571 (27.32) 38 (15.79) 486 (28.40) 47 (25.53)
1-2 1205 (8.22) 71 (14.08) 1039 (8.18) 89 (5.62)
>2 1746 (5.50) 68 (14.71) 1629 (4.97) 55 (7.27)
History of SGA
No 3442 (9.70) 170 (13.53) 3088 (9.49) 184 (9.78)
Yes 80 (21.25) 7 (42.86) 66 (16.67) 7 (42.86)
Maternal age (years)
<25 1530 (11.90) 81 (14.81) 1360 (11.69) 89 (12.36)
25-29 1216 (8.31) 58 (15.52) 1094 (7.68) 64 (12.50)
30-34 548 (7.85) 29 (10.34) 496 (8.06) 23 (0.00)
>35 228 (10.96) 9 (22.22) 94 (22.34) 15 (13.33)
Hypertensive disorders
«yes» 233(30.04) 14 (42.86) 210 (29.05) 9 (33.33)
«no» 3289 (8.54) 163 (12.27) 2944 (8.25) 182 (9.89)
Smoking
Non-smokers 3037 (9.61) 144 (13.89) 2722 (9.33) 171 (10.53)
1 2 3 4 5
Smokers 52 (13.46) 12 (16.67) 32 (12.50) 8 (12.50)
Passive smokers 433 (12.01) 21 (19.05) 400 (11.50) 12 (16.67)
Marital status
Married/civil marriage 3073 (9.70) 121 (14.05) 2811 (9.43) 142 (11.27)
Divorced/widowed 205 (11.71) 25 (16.00) 159 (11.32) 21 (9.52)
Single 244 (11.89) 31 (16.13) 184 (11.41) 28 (10.71)
Nationality
Uzbek origin 2632 (10.03) 130 (14.62) 2355 (9.43) 147 (10.20)
Others 890 (10.00) 47 (14.89) 799 (10.26) 44 (13.64)
First trimester vaginal bleeding
«yes» 260 (21.15) 20 (50.0) 227 (16.74) 13 (53.58)
«no» 3262 (9.1) 157 (10.19) 2927 (9.09) 178 (8.43)
Table 2.- Associations between maternal and fetal characteristics and SGA in the whole population of babies and in gestational age strata
SGA(general) OR (95% CI) SGA (preterm) OR (95% CI) SGA (term) OR (95% CI) SGA (posterm) OR (95% CI)
Gender: male (reference)
Female 1.42 (1.14-1.77) 1.04 (0.45-0.39) 1.43 (1.13-1.82) 1.79 (0.70-4.53)
Birth order: first (reference)
Second 0.70 (0.54-0.92) 0.63 (0.22-0.80) 0.71 (0.54-0.94) 0.59 (1.77-1.95)
Third and more 0.80 (0.61-1.04) 1.43 (0.53-0.85) 0.75 (0.56-1.01) 0.88 (0.31-2.54)
Interpregnancy interval:1-2 years (reference)
<1 4.13 (3.14-5.44) 1.14 (0.38-.43) 4.45 (3.31-.99) 5.76 (1.89-17.57)
>2 1.59 (1.19-2.12) 0.95 (0.37-0.45) 1.70 (1.24-.33) 0.76 (0.20-2.96)
History of SGA: "No" (reference)
"Yes" 2.55 (1.48-4.42) 4.79 (1.01-0.81) 1.91 (0.99-.69) 9.28 (1.74-49.41)
Maternal age: 25-29 (reference)
<25 1.46 (1.11-1.93) 1.35 (0.46-3.97) 1.47 (1.09-.98) 1.37 (0.46-4.04)
30-34 0.97 (0.65-1.43) 0.81 (0.18-3.69) 1.04 (0.69-.57)
>35 1.40 (0.87-2.25 2.00 (0.32-12.46) 1.36 (0.81-2.29) 1.35 (0.24-7.81)
Hypertensive disorders: "No" (reference)
"Yes" 4.60 (3.39-6.24 5.36 (1.69-17.06) 4.55 (3.29-6.30) 4.56 (1.05-19.79)
Smoking: Non-smokers (reference)
Smokers 1.46 (0.65-3.27 1.24 (0.25-6.08) 1.39 (0.48-3.99) 1.21 (0.144
Passive smokers 1.28 (0.94-1.76 1.46 (0.45-4.78) 1.26 (0.91-1.76 1.70 (0.35-8.38)
Marital status: Married/civil marriage (reference)
Divorced/widowed 1.24 (0.79-1.92) 1.17 (0.36-3.81) 1.23 (0.74-2.04) 0.83 (0.18-3.89)
Single 1.26 (0.84-1.89 1.18 (0.40-3.48) 1.23 (0.77-1.97) 0.95 (0.26-3.49)
Nationality: Uzbek origin (reference)
Others 1.11 (0.87-1.42) 1.39 (0.50-3.83) 1.10 (0.84-1.44) 1.39 (0.50-3.83)
First trimester vaginal bleeding: "No" (reference)
"Yes" 2.69 (1.95-3.71) 3.39 (3.19-24.38) 3.10 (1.39-2.91) 3.39 (4.04-6.26)
Discussion
Our study reassessed well known maternal and newborn risk factors for SGA applicable to Uzbekistan population. Generally we could conclude that risk factor for our population is not differ from other regions of the World. Meantime, in our study we found difference in the incidence of SGA infants depending on gestational age strata. Especially high incidence of SGA we found for preterm strata. It is in line with other studies where authors indicate that high incidence of preterm SGA can have multiple causes and one of them the way antenatal care provided [12]. The other is gender-based difference. It has been reported that boys are more likely to be born before term in a different of populations [15]. In our cohort we registered reversal findings. Odds ratio to be SGA is higher for female newborns.
We also find that short IPI of les than 1 year is a major risk factor for SGA in general cohort as well as in strata. We fully agree with authors who suggest that adverse neonatal outcomes after short IPI arise due to insufficient recovery of depleted maternal folate levels and other nutrients prior to the second pregnancy [11; 13].
The massive of evidence indicates that smoking is a major risk factors not only for low birthweight but for others serious perinatal complications. Traditionally the rate of smoking among women in Uzbekistan is quite low and according to
local authorities data is less than 1%. While the low smoking rate among women can be explained cultural features, the rate of passive smoking remains quite high. In our study we registered that passive smoking exposure was associated with SGA and we can suggest that severity of this condition has a dose-response relationship to the number of smokers in the home. In fact this reliance was confirmed by Ko TJ et al. [8] and Fantuzzi G et al. [6].
Among major risk factors of perinatal and obstetrical complications for our population we would like to mention hypertensive disorders in pregnancy. In our study, the SGA rate in women with hypertensive disorders was significantly higher, which is consistent with the results of various studies in the literature [1; 14].
In conclusion, our study aimed to describe risk factors associated with SGA for Uzbek population. We could confirm that majority of maternal and newborn characteristic, as well as abnormalities, generally associated with SGA, are applicable for women, living in Uzbekistan. At the same time we found that short interpregnancy intervls, passive smoking and hypertensive disorders are most significant factors. pregnancies and mothers with known this conditions might be followed-up more closely with respect to the increased risk of SGA.
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