Epidemiology of Adverse Outcomes in Teenage Pregnancy—A Northeastern Romanian Tertiary Referral Center

Background: Despite being a very well-documented subject in the literature, there are still conflicting results regarding teenage pregnancies and their fetal outcomes. Methods: We conducted a retrospective, comparative cohort study that included 1082 mothers aged less than 18 years, compared to 41,998 mothers aged over 18 years, who delivered in our tertiary referral center between January 2015 and December 2021. To check for significant differences between the two groups, the chi-qquared or Fisher’s test for categorical variables were used. Results: We detected statistically significant higher rates of fetal malformation, premature birth, FGR and SGA fetal growth conditions, preeclampsia, condylomatosis and vaginal infection with E. coli in our cohort of teenagers. In this subpopulation of teenagers, the rate for premature birth at less than 32 weeks of gestation was 3.26-fold higher and 3.25-fold higher for condylomatosis, and these results referred to the cohort of adult patients (>18 years old) that gave birth in the same interval of time. Conclusions: Teenage pregnancies still remain a major health problem that burdens all countries worldwide regardless of their income. It needs solutions initially to prevent pregnancy in this young age segment and last but not least to improve both maternal and fetal outcomes.


Introduction
The transitional stage of physical and psychological development from childhood to adulthood, comprising the totality of changes in social environment, mental and biological health, defines "adolescence". The World Health Organization (WHO) describes an adolescent or a teenager as those between 10 and 19 years of age [1]. It is a critical stage of development during which any stressful experience may deleteriously impact stages from adolescent development to healthy adulthood. A pregnancy can be such a stressful experience, as teenagers are not physically and mentally mature enough to experience challenges [2].
Pregnancy in adolescence is defined as teenage pregnancy between 10 and 19 years old. It is a proven fact that a pregnancy in this stage of a woman's life involves an increased risk The data regarding the young mothers were selected from the hospital's electronic health records. The gestational age was calculated as the interval between the date of delivery and the date of the last normal menstrual period, and it was adjusted by using either first or second trimester morphological scans or the only ultrasound assessment the patient underwent. The data were checked for validity or missing values and then corrected by reviewing both the mother and newborn's medical records.
All data analyzed in our statistics (blood tests, vaginal and urinary probes for culture) were obtained upon admission to our hospital.
The diagnostic criteria for the associated disorders were as follows: -Maternal anemia-a maternal hemoglobin concentration less than 11 mg/dL [16]; -Fetal growth restriction (FGR)-an estimated fetal weight at or below the 3rd percentile compared to normal fetal weight for gestational age associated with abnormal Doppler [17]; -Fetuses small for gestational age (SGA)-fetuses with birthweight less than the 10th percentile for the gestational age [18]; -Fetuses large for gestational age-birthweight >90th percentile for gestational age [19]; -Premature birth-any birth before 37 weeks of gestation [20]; -PROM (prelabor rupture of membranes)-the rupture of membranes prior to the onset of labor [21]; -Chorioamnionitis-infection of the amniotic sac and membranes [22]; -Gestational hypertension-blood pressure above 140/90 mmHg after 20 weeks in previously normotensive women without proteinuria or other signs/symptoms of preeclampsia-related organ dysfunction [15]; -Preeclampsia was defined as the new onset of hypertension and proteinuria or hypertension and significant end-organ dysfunction with/without proteinuria after 20 weeks of gestation in a previously normotensive woman/new onset of proteinuria, significant end-organ dysfunction or both after 20 weeks of gestation in a woman with chronic/pre-existing hypertension (it may also develop postpartum) [15]. -HELLP syndrome was defined as the presence of hemolysis, elevated liver enzymes and low platelets [15]; -Cholestasis of pregnancy-a liver disorder in the late second and early third trimester of pregnancy characterized by pruritus with increased serum bile acids and other liver function tests [23].
All patients signed the informed consent form, and we obtained approval from our hospital ethics committee to conduct this study (10,426/24.08.2021).

Data Analysis
SPSS for Windows version 27.0 (IBM, Armonk, NY, USA) was used for data analyses. Kolmogorov-Smirnov, Shapiro-Wilk, Student's t-test, and Mann-Whitney U were used were used for descriptive statistics.
We performed a descriptive statistical analysis using the Statistical Package for the Social Sciences (version 29.0.0.0, IBM Corp., Armonk, NY, USA). Categorical variables were counted and expressed as frequencies.
To check for significant differences between the two groups (adolescent underage pregnant women versus control group), the chi-square or Fisher's test for categorical variables were used. A two-tailed p-value < 0.05 was considered significant. The risks were estimated using Fisher's exact test with a p-value and 95% Confidence Interval (CI).

Results
During the study period, 2015-2021, of the 43,080 women who were admitted and gave birth in the Iasi "Cuza Voda" University Hospital, 41,998 (97.49%) were adults and Figure 1 shows the trend of teenagers who gave birth during this 7-year study in our tertiary referral center, and Tables 1 and 2 show their age distributions. Teenagers more frequently came from rural areas, and the difference was statically significant at p = 0.037.

Results
During the study period, 2015-2021, of the 43,080 women who were admitted and gave birth in the Iasi "Cuza Voda" University Hospital, 41,998 (97,49%) were adults and 1082 (2.51%) were underage adolescents. Figure 1 shows the trend of teenagers who gave birth during this 7-year study in our tertiary referral center, and Tables 1 and 2 show their age distributions. Teenagers more frequently came from rural areas, and the difference was statically significant at p = 0.037.    There was a decline in the rate of teenage pregnant women from 2015 to 2019, with 2019 being the year with the lowest teenage pregnancy rate in our hospital (119 cases-11%). During the two pandemic years that followed, the rates of teenage pregnancies showed an upward trend compared to 2019.
There were 141 recurrent teenage pregnancies, with the majority of our minor patients being, as expected, primiparous. In Romania, teenage pregnant women who have no control of their fertility remain exposed to recurrent, closely spaced pregnancies and to all inherent unfavorable outcomes. In the present study, the percentage of multiparous teenagers was 9.1%, while 0.3% of the pregnant teenagers delivered three children between the age of 12 and 17 years.
The abortion rate in these cases was low at 46 cases, accounting for only 4.3% of all teenagers. In 60% of these cases, elective pregnancy termination was performed, with only 40% being spontaneous first trimester abortions or miscarriages.

Fetal Malformations
We identified 25 cases of fetal malformations, representing 2.3% of the 1082 minor adolescents who gave birth in our hospital. The types of malformations detected are listed in Table 3.

Twin Pregnancy
We identified 10 cases of twin pregnancy, representing 0.9% of our subpopulation group. The type of twin pregnancy and also the complications that occurred during the pregnancy are described in Table 4.

Maternal Anemia
Maternal anemia was detected based on antepartum hemoglobin and hematocrit levels in 627 young patients, with a difference in hemoglobin and hematocrit levels between pregnant women with and without anemia exhibiting a p value of less than 0.001.

Fetal Growth Pathology (FGR, LGA, SGA)
In total, 96 cases of fetal growth restriction (8.9%), 88 cases of fetuses that were small for gestational age (8.1%) and 28 cases of fetuses that were large for gestational age (2.6%) were detected. In establishing this diagnosis with accuracy, we also used the Ballard neonatal scores.
3.1.5. Premature Birth and/or PROM One hundred sixty of our patients gave birth prematurely, representing 14.8% of all teenage pregnant women, with forty-four (4.1%) of them at less than 32 weeks gestational age. We found no statistically significant difference between rural and urban residents in the percentage of premature births in teenage mothers (p-0.201). In six cases (0.6%), chorioamnionitis was detected (Table 5). Only 69 patients had urinary tract infections, which account for 6.4% of all teenage pregnancies. The most commonly involved microorganisms were as expected: Escherichia coli (43 cases-4%) and Enterococcus (8 cases-0.7%).

Other Conditions (Cholestasis of Pregnancy, Condylomatosis and Infection with Hepatitis B and HIV)
We found three cases of hepatitis B infection (0.3%), one case of HIV infection (0.1%) and eight cases of cholestasis of pregnancy (0.7%). We also noticed a high rate of condylomatosis in this young population, and it was statistically significant in more cases than in the adult pregnant women group with a p value less than 0.001.
When the outcomes and complications in the cohort of pregnant teenagers who gave birth in our hospital during the 7-year study were compared with the cohort of women over 18 years old that gave birth during the same interval in our hospital, we found some interesting results (Table 6).
We also noticed a high rate of condylomatosis in this young population, and it was statistically significant in more cases than in the adult pregnant women group with a p value less than 0.001.
We detected statistically significant higher rates of fetal malformation, premature birth, FGR and SGA fetal growth conditions, preeclampsia, condylomatosis and vaginal infection with E. coli in our cohort of teenagers (Table 6). In this subpopulation, the rate for premature birth at less than 32 weeks gestation was 3.26-fold higher (95% CI, 1.84-5.76, 95%), and for condylomatosis, it was 3.25-fold higher (95% CI, 1.80-5.89, 95%). These risks were estimated using the p-value from Fisher's exact test.

Discussion
Teenage pregnancy is associated with many risks concerning both the life of the young mother and her baby. Pregnancy can negatively impact a variety of aspects of a young mother's life, such as health, education and/or future employment perspectives [24]. Data from the literature reveal that teenage pregnancy poses high-risks [25] as a result of a combination of factors: the biological immaturity of teenagers, a lack of sexual education or lack of accessibility to it, poor perinatal care (mostly in low-income countries or lack of healthcare providers), inadequate maternal nutrition and last but not least stress with its multiple negative effects. Low literacy likewise comports the risk of unappropriated health decisions and access to available healthcare services, and it comprises well-recognized and continuous source of unfavorable maternal and fetal outcomes [26].
Teenage birth rates dropped to 7% in teenage girls aged between 15 and 17 years and dropped to 4% for older teenagers between 18 and 19 years in the United States. [27]. In Romania, where data on teenage births are incomplete, the incidence is around 3.7% according to Sedgh et al. [28].
In Romania, teenage pregnant women who have no control of their fertility remain exposed to recurrent, closely spaced pregnancies and to all inherent unfavorable outcomes.

Malformations
In our study, the rate of fetal congenital malformation among teenage mothers under 18 years of age was lower than in previous studies in the literature [29][30][31], although some studies report higher rates of fetal congenital malformations in very young (13-16 years) and young teenagers (17-18 years) [29,30]. Even though the studies offer conflicting results reporting higher incidences of gastroschisis and polydactyly or cardiac defects, we found that more than half of the cases had plurimalformative fetuses (14 cases of a total of 25) [31].

Twin Pregnancy
A study of twin birth rates in Europe by Heino et al. underlined the marked variations between countries, with a median twin birth rate of 1.68%. Our country has the lowest twin birth rate (0.9%) [32]. In our cohort of teenage women, the incidence of twin birth was 0.9%, which is similar to that reported in the above-mentioned study, and in our tertiary referral center, the incidence of twin pregnancy in adult population was 2.41%. The higher incidence of twin pregnancies and twin births in adult women could be explained by an increase in the number of pregnancies obtained by using assisted reproductive technology and the older age of first-time mothers [33].

Maternal Anemia
Maternal anemia seems to be the most-mentioned teenage pregnancy complication in the literature [34]. In our study, this condition was statistical insignificant, and it was slightly more prevalent in our teenage pregnancy group than in pregnant adult women (p = 0.222). According to some studies, the younger the teenage pregnant woman, the lower her hemoglobin level will be due to the necessary higher intake to assure the intense biological processes of both the young mother and the fetus [35,36].
Nevertheless, the high incidence of anemia detected in both groups underlines another serious medical problem that seems to be underestimated and poorly managed. More than 50% of our pregnant women in both our groups had anemia. The high percentage is close to the one detected by Ampiah et al. in their study in rural areas from Ghana [37]. Even though one might consider it to be less important than other conditions, anemia is a leading cause of maternal death and adverse pregnancy outcomes. Resulting from an association of multiple factors such as infections, nutrition deficiency and a lack of correct supplementation, anemia determines premature birth, low birth weight (FGR or SGA) and even low Apgar scores. Many studies underlined the correlation between maternal anemia and premature birth [15][16][17][18], and the correlation is a major source of increased neonatal morbidity and mortality. Moreover, anemia leading to FGR and SGA birth is involved in unfavorable fetal outcomes with high morbidity and mortality [17,18,36,38,39].

Fetal Growth Pathology
Many studies state that a growing organism does not efficiently mobilize fat reserves as an adult organism to adequately sustain fetal growth, generating impairments, and the pregnancy itself is affected by the mother's competitive continued growth [40]. The data from our study are in agreement with those reported by Nkwabong et al. and Agbor et al., showing that the mean birth weight was smaller among teenagers than adult pregnant women, increasing with age [41,42]. Moreover, anemia might have a negative impact on fetal growth, causing both FGR or SGA birth, as stated before. A proper prenatal care with correct management and the mending of teenage mother's anemia might reduce the number of preterm deliveries and FGR or SGA [17,36,37].
Moreover, our study identified a statistically significant lower proportion of LGA fetuses, and this is similar to other studies in the literature. As a possible explanation for these results, both Jain et al. and Karai et al. stated that very young mothers have lower obesity and lower glucose impairment and gestational diabetes incidence, all three of of which are involved in higher percentile fetal growth [31,43].

Preterm Birth and PROM
The incidence of premature birth and especially of premature birth before 32 weeks gestation was significantly higher in our adolescent group compared with adult women. Premature birth is sub-classified into three groups: extremely preterm birth (<28 weeks gestation), very preterm birth (between 28 and 32 weeks of gestation) and late preterm birth (between 32 and 37 weeks of gestation). Preterm birth and PROM) share similar multifactorial etiopathogenesis. An incompletely developed cervix will be less resistant to clinical and subclinical infections. Infections initiate prostaglandin production, with prematurely ruptured membranes causing premature birth [43]. Moreover, the high incidences of deficient prenatal care with a delayed recognition of pregnancy and its possible complications are involved in both premature birth and PROM. Our results are similar with those reported by Fleming et al. and Jain et al. [43,44].
Premature birth continues to be a serious burden on our healthcare system, implying great costs and also being responsible for high morbidity and mortality, especially in middleincome countries such as Romania. Low birth weight and prematurity are responsible for the death of about 40% of the children under 5 years old worldwide [45].
The mean gestational age at childbirth in our underage adolescents was similar in both rural and urban areas (38.0 weeks of gestation in rural areas and 37.7 weeks in urban areas).

Maternal Infections
Underage pregnant adolescents are more prone toward contracting vaginal infections and sexually transmitted diseases. In our study, the analyzed subpopulation group presented a high incidence of E. coli vaginal infection, probably due to poor hygiene and health education. Vaginal infection was present in 44.5% of the teenagers in our study, statistically significantly higher than in the adult pregnant women group (p < 0.001) with respect to E. coli vaginal infection [1].
Although studies show that urinary infections are more frequent among pregnant teenagers, in our study only 6.4% of our patients had this associated pathology. As expected, based on our previous findings over half of these infections were due to E. coli. The rate is lower than that reported by Santos et al. in their study, and as to their frequency in underage adolescent pregnancies, it was less commonly encountered than anemia in our group of pregnant women [46].
Maternal vaginal and urinary infections are associated with premature birth and PROM, and these are well-known causes of maternal and fetal morbidity and mortality.

Hypertensive Disorders
Another spectrum of medical conditions that include a continuous and well-recognized cause of iatrogenic premature birth involves hypertensive disorders, including gestational hypertension, preeclampsia, eclampsia and HELLP syndrome. Amoadu et al. in their 2022 study reported high rates of hypertensive disorders and premature spontaneous and iatrogenic births in teenage pregnancies in both high and low-income countries [47,48]. A possible explanation for preterm births in pregnancies with hypertensive disorders might result from the consequent characteristic utero-placental ischemia [15,20,48].
Neal et al. state that this associated pathology is a major factor that strongly negatively impacts young maternal death, a finding that is also supported by the Finnish study by Leppalahti et al. 2013 [49,50]. Some other studies from Africa, Asia and South America that evaluated populations that were different from ours do not sustain this strong association between young adolescent pregnancy and adverse maternal outcomes due to racial and ethnic characteristics, such as the hypertensive disorder spectrum [6,10,15,26,47].
The number of preeclampsia cases was statistically significantly higher in our teenage cohort than in the adult pregnancy group (p < 0.001), whereas the rates of pregnancy hypertension and HELLP syndrome were statistically significantly higher in the adult women group. Although the percentage of patients with hypertensive disorders is higher in young nulliparous women, as expected, not all the studies in the literature agree, and their results are conflicting. A great number of studies support the observation that the hypertensive disorder spectrum complicates more teenage pregnancies than adult ones [31,33]. On the other hand, studies conducted in Oman and Canada found no statistically significant differences between young and adult mothers concerning the hypertensive disorder spectrum, and this might be due to sample sizes and social and biological risk factors [25,31,43].

Other Conditions (Cholestasis of Pregnancy, Condylomatosis, Hepatitis B and HIV Infection)
Of these diseases, only condylomatosis had a statistically significant higher rate in young adolescent mothers with a p value of under 0.001. Higher rates were also found only in the adult women group.
The limitations of our study are the following: its retrospective character and the sample size that originates from a single tertiary center in our region. No data about the adolescents' level of education, income, vitamin supplementation, nutrition and smoking or drug abuse habits were collected.
The strength of this research study is the large sample size obtained from the tertiary referral center database and the continuous verification for validity data, which mirrors obstetricians' observations with respect to the effect of young maternal age on maternal and fetal outcomes in our region. Our results have markedly important implications, especially due to the fact that our country has incomplete data about this major health problem that has indisputable socioeconomic impacts on our health system.

Conclusions
Teenage pregnancies still remain a major health problem that burdens all countries worldwide regardless of their income. The problem requires solutions to prevent pregnancies in this young age segment and to improve both maternal and fetal outcomes. This particular stage in a woman's development remains a critical one requiring more attention and sustained effort from parents, schools and governments. The higher the incidence of pregnancy in this population segment, the higher the need of a country or region to take measures to improve the quality of education and the healthcare system.
Our study provides obstetricians with new insights into the particularities of underage adolescent pregnancy in our country and formulates directions for actions in order to improve our healthcare system. The major healthcare problems that we identified were as follows: a high incidence of anemia in our teenage pregnant women with its well-known complications and high incidences of premature birth, infections, preeclampsia and fetal growth pathology (SGA and FGR) in our young teenagers. All these conditions contribute to rising fetal and neonatal morbidity and mortality and all its related costs in our middleincome healthcare system. The rate of young adolescent pregnancies can be considered a reflection of the healthcare system in a country. Thus, in order improve the healthcare system, we need to focus on shifting from individual policies and actions to actions and policies that address both social and environmental structures.

Institutional Review Board Statement:
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of "Cuza Voda" University Hospital (10426/24 August 2021).

Informed Consent Statement:
Written informed consent has been obtained from patients to publish this paper.

Data Availability Statement:
The data used to support the findings of this study are available upon request.

Conflicts of Interest:
The authors declare no conflict of interest.