1- INTRODUCTION

Fetal development in the uterus is a strong predictor of the neonate's survival after birth and poor fetal development is a health risk factor in infancy and adulthood. In addition to reduced neonatal survival, poor fetal development is associated with complications in adulthood, including chronic diseases such as cardiovascular disorders, diabetes, hypertension, and dyslipidemia, and growth-developmental and psychological disorders [1]. The anthropometric indices are considered as the least expensive and most applicable non-invasive method for measuring fetal development. Birth weight is the most used anthropometric index at birth. Head circumference (HC) and length can also be helpful in determining fetal development. Infant's reduced HC and Chest Circumference (CC) and length affect their weight and cause Low Birth Weight (LBW) [2]. LBW is regarded as the leading cause of infant mortality. The high mortality rate in LBW infants is mainly caused by the increased incidence of infection, asphyxia, and emergency surgeries [3]. Other complications of LBW include increased rate of neonatal jaundice, respiratory distress syndrome, hypothermia, hypoglycemia, necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH) [4]. LBW may be either caused by preterm delivery or the infant being small for gestational age (SGA), or a combination of both. However, LBW as well as abnormality of other anthropometric indices have also been seen in term pregnancies, which indicates unfavorable uterine conditions for fetal development [5 and 6]. Reducing LBW by 30% between 2012 and 2025 is among the goals of the World Health Organization, but its descending trend has been much slower than expected (1% annually instead of 3%) [7]. Acquiring the knowledge of factors associated with fetal development can be the first step in initiating research and interventions to improve the fetal status, including reducing LBW. Among the important factors that may affect fetal development is the maternal condition during pregnancy, which in other words can be referred to as prenatal factors. Study results do not concur in terms of the role of prenatal factors in fetal development. For example, some studies have revealed the relationship of fetal development with maternal nutrition as measured by two indicators of anemia and BMI [8-11]. The results of a study by Mahmood et al. (2019) showed that maternal anemia in the third trimester is associated with all perinatal complications including LBW, SGA, preterm childbirth, and fetal and neonatal death [12]. In another study by Naoko et al. (2012), the relationship between LBW and maternal anemia was observed only in mothers with severe anemia [13]. However, some other articles rejected the relationship between maternal anemia and LBW, and argued that other maternal factors occurring besides anemia can affect the fetal development parameters; therefore, they recommended that other influential maternal factors such as BMI, parity, chronic diseases, and lifestyle be investigated along with anemia [10 and 14]. Fetal development has been shown to have relationships with other factors, including prenatal chronic diseases such as thyroid problems, diabetes, as well as prenatal complications such as blood pressure disorders and urinary tract problems [10 and 15]. Furthermore, research has shown that maternal BMI can have a role in the intensity of LBW, preterm childbirth, and IUGR [16 and 17]. A meta-analysis by Zhen Han assessed the relationship between maternal BMI and LBW, and reported a direct relationship between them; this result was observed in both developed and developing countries [18]. Although this index is measured and recorded for all pregnant mothers in all clinics and health centers, it is not much considered in predicting the pregnancy outcomes, and its effect on LBW is ignored [17]. We know that the frequency of factors which may affect fetal growth differs from one society to another. Furthermore, the results about the relationship of prenatal problems with fetal development indices are contradictory, and no study has yet been conducted in the city of Bushehr on the frequency of prenatal problems and their relationships with neonatal anthropometric indices. The present study, therefore, aimed at investigating certain prenatal problems and their relationship with neonatal anthropometric indices at birth.

2- MATERIALS AND MEDODS

The present cross-sectional descriptive-analytical study was conducted using registered records in Iran’s Integrated Health System, locally known as SIB. SIB was launched in 2016 to register all healthcare services. The records of 616 pregnant mothers who had given birth during 2017-18 in the city of Bushehr (Iran), with SIB-registered details of them and their infants from the first prenatal visit to the first postpartum visit were reviewed. Out of the comprehensive healthcare centers, five were randomly selected, and all records of eligible mothers were reviewed. The available records exceeded the sample size needed for regression analysis (10 to 30 subjects per predictor variable). The study inclusion criteria were having registered records during 2017-18, mother’s age of 18-40 years, and singleton pregnancy. The exclusion criteria were mother's use of tobacco or cigarettes, gestational age of Table 2. The results of univariate and multivariate regression analyses are shown in Tables 3 and 4. Based on the multivariate regression analysis, multiparity, gestational age, and neonatal male gender had direct relationships and vaginal childbirth an inverse and significant relationship with the neonate's HC. Mother's BMI in the first perinatal visit and gestational age had direct and significant relationships with weight-for-age Z-score and length-for-age Z-score. Furthermore, neonatal gender (male) had an inverse and significant relationship with length-for-age Z-score.

4-DISCUSSION

Fetal development and its related factors can provide a basis for prenatal planning to reduce fetal development retardation and its consequences. The present study was conducted in the city of Bushehr to investigate prenatal factors and their relationships with the infant's anthropometric indices at birth.

Based on the data analysis results, LBW was 4% in the present study, while it has been reported 7% in the neighboring province: Fars province [19]. This difference can be attributed to the study target groups. In the study conducted in Fars province, LBW included term and preterm childbirths, but in the present study, only term infants were considered. Different studies have reported different LBW rates, for example, a study in Tabriz reported the prevalence of LBW 5.1%, which is closer to that of the present study [20]. Studies conducted in Lebanon, Bangladesh, and Nigeria reported LBW as 2.5%, 11.6%, and 7.3%, respectively [8, 21, and 22], which are not in agreement with the results of the present study. This difference can be partly attributed to the study method, including definition of LBW, and inclusion or exclusion of preterm childbirth, and partly to the difference in communities, since fetal development differs from one population to another [23]. In the present study, anemia was observed in 16.2% of the cases in the first trimester and in 22.5% during the second. A study conducted in another city in Bushehr province reported the prevalence of anemia as18% in the first trimester and close to 31% in the second [24], which is close to the present study results in relation to the first trimester anemia. However, the prevalence of anemia reported in that study exceeded that in the present study for the second trimester. This difference is supposed to be due to the definition of anemia. In the mentioned study, anemia was defined as Hb

Moreover, findings revealed that the first and the second trimester anemia had no relationship with any of the anthropometric indices. However, the infant's length and weight were correlated with gestational age and maternal BMI. Anthropometric indices had no relationship with other prenatal problems such as urinary tract infection, hypothyroidism, and diabetes. Various studies have reported conflicting results with regard to the relationship of anemia with neonatal HC and its lack of a relationship with other indices. In agreement with the present study, Saraswathi et al. (2019) reported that maternal Hb has no relationship with neonatal HC and length [11]. However, a relationship between maternal anemia in the first trimester and IUGR was shown in a meta-analysis [29]. Srinivas et al. (2015) reported no relationship between anemia and LBW [30]. The discrepancy in results related to the relationship between anemia and anthropometric indices can be attributed to different study methods, different definition of anemia, neglecting duration of suffering anemia, neglecting confounding factors, and even type of statistical analysis, and especially genetic differences. It seems that further prospective studies can find more accurate results in terms of the effect of anemia on the fetal status. In the present study, duration of suffering anemia was not available, and the third trimester anemia was not investigated. The results of some studies suggest that anemia in the second and the third trimesters, and not in the first trimester, can increase LBW and even cause preterm childbirth [27]. In the present study, mean Hb was not very low, even in those with anemia, suggesting mild anemia. Study results suggest that reduction in infant's anthropometric indices happens in mothers with severe anemia [28 and 31]. It has been argued that Hb between 9-9.5g/dl does not cause any neonatal LBW, and women with Hb

In the present study, no significant difference was found in anthropometric indices between the mothers with insulin-dependent diabetes, gestational diabetes or hypothyroidism or abnormal urinary analysis in the first or the second trimester and the mothers who did not suffer any of these disorders.

Though a meta-analysis had shown a correlation between maternal diabetes and increased neonatal fat mass [32], the fat mass, free fat and thickness of scapular skin fold were identified as fat indicators in the present study. Furthermore, controlled or uncontrolled diabetes was not discussed. Au et al. argued that by controlling diabetes in diabetic mothers, fat mass in their infants would not be different from that in non-diabetic mothers. The fetal fat accumulation can be corrected by correcting maternal glucose and normal glucose (gestational diabetes control) [33]. In the present study, the participants’ blood glucose had been controlled with insulin or diet.

In the present study, no relationship was found between controlled hypothyroidism and anthropometric indices. In a meta-analysis investigating thyroid function, measurement of iodine (a precursor to thyroid hormones) was used, and no linear or non-linear relationship was observed between iodine level and neonatal anthropometric indices [34]. A similar study also reached the same result [35]. A study showed that neonatal serum TSH had a relationship with growth parameters at birth [36], and accordingly, the difference may be due to hypothyroidism being controlled or uncontrolled and acquiring hypothyroidism, i.e., if hypothyroidism is severe enough to affect neonatal TSH, it can affect neonatal parameters.

Regarding abnormal urinalysis and its lack of relationship with anthropometric indices, the present study results confirm those obtained by Alijahan et al. (2013), who found no significant relationship between urinary tract infection and LBW [37]. In another study, mother's urinary tract infection was not different between term and late preterm infants [38]. In contrast, most studies have shown that mother's urinary tract infection, especially pyelonephritis can cause premature rupture of membrane/ preterm labor, and IUGR [39-41]. In the present study, all infants were term, and it was not possible to investigate the effect of urinary problems on preterm childbirth, which may explain the lack of a relationship between urinary tract infection and LBW. Given the previous studies results, positive urinary culture, especially the presence of pyelonephritis appears to be a factor for adverse pregnancy and neonatal outcomes rather than abnormal urinalysis. In the present study, abnormal urinalysis included bacteriuria and pyuria. In most cases in the present study, the results of urine culture were not available; there were only a handful of results showing positive cultures, which could not be included in the analysis, due to their limited number. Moreover, their records did not contain information on whether those with abnormal urinalysis had asymptomatic or symptomatic bacteriuria. Accurate recordings of urinalysis including whether they had a culture, the results of culture, microorganisms reported in the culture, and patient follow-up outcomes can help assess and manage the effects of urinary tract infections.

Other factors affecting anthropometric indices including BMI and GA, which were found in this study to have a relationship with neonatal weight and length, were similar to those found in other studies [2, 16, and 42]. With regard to GA, although all mothers had term pregnancies and preterm infants were excluded, that range of term pregnancy can itself affect neonatal weight. Maternal BMI is associated with neonatal weight, which is not surprising, because fetal development is a function of maternal nutrition. The mother's anthropometric features can be a good indicator of the fetus growth [17].

Multiparity was found to have a positive correlation with neonatal HC; and vaginal childbirth was negatively correlated with it, which is not odd. Other studies have also shown bigger HC in multiparous women [43-45]. Childbirth is faster in multiparous women, and changes in the fetal head that reduce HC do not happen. Besides, multiparous mothers have larger fetuses. Moreover, HC is smaller in vaginal childbirths compared to cesarean; despite a large head is probably a reason for cesarean section rather than type of childbirth affecting the head. Studies have shown that large biparietal diameter is associated with increased odds of cesarean section and instrumental childbirth [46 and 47]. However, vaginal childbirth and the fetal head passing through the birth canal causes a series of changes on the fetal head, including molding, which changes the size of HC.

Interestingly, in the present study, an inverse relationship was observed between the infant's male gender and length-for-age Z-score. Meanwhile, previous studies have shown bigger length, weight and HC in male compared to female infants [48]. In the present study, the length-for-age Z-score was used, which adjusts length to gender; and, therefore, there should be no difference between boys and girls, and this inverse relationship probably shows that standardization in any society should be in accordance with that society's attributes, and standardizing based on infants in one country cannot be generalized to another.

5- CONCLUSION

Generally, the present study showed a prevalence of prenatal complications such as anemia among the study population, although it was mostly mild anemia. The prenatal complications had no relationship with anthropometric indices, which were mostly due to the complications being controlled or mild. Moreover, some of the results require further investigations to be accepted or rejected. The mother's BMI can be a predictor of fetal growth and should be addressed more in prenatal clinics. The inverse relationship of male gender with length-for-age Z-score indicates the need for standardization of anthropometric indices in each society.

6- SUGGESTIONS & LIMITATIONS

The present paper, being the first research addressing the relationship between the prenatal complications and anthropometric indices in the city of Bushehr, undergoes certain limitations. Firstly, this study was a retrospective one based on the registered records, and some indices needed for better analysis and outcomes had not been registered. Longitudinal studies to obtain more accurate results are recommended. Secondly, With regard to some complications such as thyroid disorder, there were only a handful of cases showing one end of the complication, namely hyperthyroidism, which could not be included in the analysis. So, the few records in which mothers had hyperthyroidism were excluded. A study with a larger sample size can help assess less prevalent complications. Another important limitation was the difference between the accuracy levels of the measurement tools applied in different centers, which might have affected the registered infant's anthropometric indices and the prenatal disorders used in this study.

7- ACKNOWLEDGEMENTS

The authors wish to thank the research deputy and student research committee of Bushehr University of Medical Sciences for funding this research project, and all professors for their ongoing cooperation in this study.

8- CONFLICT OF INTEREST: No conflict interest

9- ABBREVIATIONS

LBW: Low Birth Weight

NEC: Necrotizing Enterocolitis

IVH: Intraventricular Hemorrhage

BMI: Body Mass Index

SGA: Small for Gestational Age

IUGR: Intrauterine Growth Restriction

Hb: Hemoglobin Concentration

TSH: Thyroid Stimulating Hormone

PROM: Premature Rupture of Membranes

PTL: Preterm Labor