We designed our research as an ambidirectional cohort study that was conducted on the population of pregnant women whose pregnancy was monitored at the Clinic for Gynecology and Obstetrics of the University Clinical Centre Kragujevac, Serbia. All pregnant women with pregnancies confirmed by a gynecology specialist were taken into account, with the exception of pregnant women under the age of 18, functionally illiterate pregnant women and those with a confirmed high risk of genetic abnormalities of the fetus by a combination of ultrasound and biochemical examination during the 12th week of pregnancy. Our major outcome measures were body weight, body length and head circumference of newborns at birth. We examined the potential impact of the following variables to the newborn body size: demographic factors, presence of acute or chronic diseases during pregnancy, medications used during pregnancy, pregnancy factors, presence of uterine or placental abnormalities and maternal nutrition. For the assessment of the nutritional status of pregnant women, we previously developed and validated a special questionnaire that we named Balkan Food Quality and Diversity in Pregnancy Questionnaire-18 (BFQDPQ-18) [6]. We used the method of multiple linear regression analysis to evaluate the influence of potential factors on birth weight, length, and head circumference.

The study included 320 pregnant women with an average age of 30.35±5.50 years and 332 newborns (12 pairs of twins). At least one acute or chronic disease was diagnosed in 247 pregnant women (75.3%). The most frequently diagnosed diseases were thrombophilia (22.2%), colpitis (19.1%), hypertension (18.4%), anemia (12.2%), diabetes mellitus (11.3%), proteinuria (10.6%), and hypothyroidism (9.7%). The most commonly used drugs among our participants were antibiotic drugs (34.7%), progesterone, (28.1%), anticoagulant drugs (24.1%), calcium channel blockers (17.5%), antifungal drugs (16.6%), methyldopa (15.9%) and corticosteroids (11.9%). Four factors had a significant negative effect on birth weight: smoking (B= –196.647;p=0.002), twin pregnancy (B= –434.109;p=0.000), use of methyldopa (B= –145.561;p=0.033) and corticosteroids during pregnancy (B= –287.921;p=0.001). Smoking (B= –0.813;p=0.028), twin pregnancy (B= –1.719;p=0.005) and corticosteroid use during pregnancy (B= – 1.818;p=0.000) also had a significant negative effect on birth length. Negative effect on fetal head circumference at birth had smoking (B= –0.585;p=0.011), use of corticosteroids (B= –0.961;p=0.003) and antibiotics during pregnancy (B= – 0.547;p=0.009). Maternal height and gestational age at birth showed a positive influence on weight, length and head circumference of newborns, while pregnant women age was another factor in positive correlation with head circumference at birth.

Corticosteroids are widely used in pregnancy [7]. However, the negative effects of corticosteroids on cell growth and deoxyribonucleic acid replication are well known and described [8]. The results of a large population study conducted in Finland showed that fetuses exposed to antenatal corticosteroids during pregnancy had significantly lower body weight, body length, body mass index, and head circumference at birth compared to newborns that were not exposed to the effects of these drugs [9]. The negative effect of corticosteroids on infant body length and head circumference at birth was also noted by Thorp et al. in their retrospective study, in which they analyzed the impact of antenatal corticosteroid administration on infants treated in 100 different neonatal intensive care units in the USA [10]. Also, there is evidence indicating the teratogenic potential of corticosteroids and the association between the systemic use of corticosteroids during the period of organogenesis and the occurrence of cleft lip and palate in the fetus [7].

Hypertensive disorders are common in pregnancy and require urgent and adequate treatment [11,12]. According to the official guidelines of gynecological associations, methyldopa is the antihypertensive drug of first choice in pregnancy because it has no proven teratogenic potential [13]. However, it seems that the use of methyldopa during pregnancy is not entirely without risk to the fetus. Thus, Hoeltzenbein et al. showed that newborns of methyldopa-treated mothers had a higher rate of reduced birth weight after adjustment for sex and gestational age at birth and a smaller head circumference in male newborns [14]. Similarly, Orbach et al. noticed a negative influence of methyldopa on the body weight of newborns of both genders [15], which is in accordance with our results.

Inadequately treated urinary infections in pregnancy pose a great risk to the fetus, as they are associated with an increased risk of spontaneous abortions, premature births, and low birth weight newborns [16,17]. The results of epidemiological studies that examined the potential impact of maternal antibiotic therapy on fetal growth and development parameters are quite controversial. Thus, the results of some studies showed that the use of antibiotics during pregnancy was accompanied by an increase in the body weight of newborns at birth [18,19], while other authors came to the opposite conclusion, indicating that newborns whose mothers used antibiotics during pregnancy had a lower body weight at birth [20,21].

In conclusion, clinicians should pay special attention to pregnant women who use corticosteroids, methyldopa, and antibiotics during pregnancy in order to prevent smaller values of newborn birth size parameters. Keywords : Newborn birth size; birth weight; birth lenght; birth head circumference; drugs