Adverse Neonatal Birth Outcomes Among Adolescent Pregnancies in Kampala, Uganda Between 2015 –2018

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and older mothers (age 20-34 years) in four urban hospitals. Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% Condence Intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to older mothers. Results: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI: 1.06-1.23), low birth weight (aOR: 1.46; CI: 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI: 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI: 1.02-1.76), specically, gastroschisis (aOR: 3.20; CI: 1.12-9.13) compared to older mothers. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI: 3.7-14.3) was statistically signicant when compared to older mothers (1.6 per 10,000 births; 95% CI: 0.9-2.6). Conclusions: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to older mothers, similar to ndings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population. external birth defects, between adolescents (age 12–19 years) and older mothers (age 20–34 years) in four urban hospitals. All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes. 100,189 were among adolescent mothers and among mothers. infant preterm delivery, low birthweight, early neonatal death, external birth Adolescent pregnancies were also associated with an increased of gastroschisis when compared to older mothers.


Introduction
Pregnancies among [15][16][17][18][19] year old females account for 16 million (11%) births worldwide yet they contribute to 23% of the maternal disease burden attributed to pregnancy and childbirth. [1,2] The highest prevalence of adolescent pregnancy is found in the sub-Saharan African region, with birth rates of 101 births per 1,000 females aged 15-19 years in 2018, higher than the global adolescent birth rate of 44 per 1,000. [3] Uganda has one of the youngest populations in sub-Saharan Africa, with children and adolescents 12-19 years constituting more than half (55%) of the population in 2014, [4] and one of the highest adolescent pregnancy rates (25%) in sub-Saharan Africa. [5] Despite a decline in the fertility rate in Uganda from 6.9 in 2000 to 5.4 in 2016, and an increase in the use of modern contraception from 18% in 2000 to 35% in 2016, adolescent pregnancy remains a challenge with only 7.6% of adolescents having access to contraceptives. [5] Although previous studies have generally found a higher risk of adverse birth outcomes such as preterm birth, low birthweight (LBW), early neonatal deaths (ENND), and birth defects associated with adolescent births, [1,[6][7][8][9][10][11][12], few have been conducted in developing countries of sub-Saharan Africa. In addition, the conclusions of these studies were drawn based on data collected from small sample sizes [13] and therefore may not be representative of the general population. Most studies [9,13] that have reported birth outcomes among adolescent pregnancies in Sub-Saharan Africa have not reported the magnitude of major external birth defects. Therefore, using a large dataset obtained from an ongoing hospital-based birth defect surveillance study, we compared the occurrence of adverse birth outcomes (preterm birth, LBW, and ENND), including the rates and prevalence of speci c major external birth defects among adolescent mothers (12-19 years) and older mothers (20-34 years) in Uganda, a low-middle income setting. The ndings from this study would therefore be used as a benchmark for researchers and policymakers to understand the current estimate of the burden of adverse birth outcomes among adolescent pregnancies in a low-income Sub-Saharan African country.

Methods
We extracted and analyzed veri ed data collected between August 2015 and December 2018 from an ongoing birth defects surveillance system implemented at four major hospitals in Kampala, Uganda. [14] These hospitals have approximately 50,000 births annually, which make up more than 55% of all births in Kampala. The details of the birth defects surveillance system are described elsewhere. [14] Brie y, this birth defects surveillance system collected information from hospital records including: demographic (maternal age, delivery site), maternal health (maternal HIV status, obstetric history), and birth outcome (mode of delivery, pregnancy outcome, infant sex, gestational age, and infant examinations). Information on maternal HIV status and antiretroviral therapy was obtained from antenatal records and inpatient hospital records. Information on all live births, stillbirths, and spontaneous abortions was collected between the time of birth and discharge which usually occurs within the rst 24 hours after delivery. [14] Infants born outside the four hospitals and uninformative macerated stillbirths were not included in the surveillance system.
We de ned adolescent births as those occurring in women 12-19 years of age at delivery and births among older women as those occurring in women 20-34 years of age at delivery. There were no births to women younger than 12 years of age. We de ned gestational age as the interval between the date of delivery and the last menstrual period (LMP) in completed weeks; if the LMP was unknown or missing, a clinical estimate of gestational age was used, such as estimates from fundal height or abdominal ultrasound. We de ned preterm delivery as live births occurring at gestations of less than 37 weeks. Low birth weight (LBW) was de ned as an infant weighing less than 2,500 g measured within 24 hours after birth using digital scales among term (≥ 37 weeks) live births. Early neonatal death (ENND) was de ned as death among live neonates born at term during the rst 48 hours or before the mother was discharged from the hospital. Stillbirth was de ned as a baby born with no signs of life at or after 28 weeks' gestation, while a spontaneous abortion was de ned as fetal death at less than 28 weeks' gestation.
Birth defects were con rmed through bedside examination by a physician and review of photographs, narrative descriptions, and or drawings by a birth defects expert who veri ed or reassigned the diagnosis code. Details of the birth defect ascertainment and classi cation have been described previously. [14] Data were analyzed using STATA version 15 statistical software (StataCorp. 2017. College Station, TX: StataCorp LLC). Descriptive statistics of maternal and infant characteristics by maternal age group were calculated as frequencies and percentages, and the differences between proportions were tested with Pearson's chi-square test.
We used multivariable logistic regression analysis to estimate crude and adjusted odds ratios (cORs and aORs, respectively) along with their 95% con dence intervals (CIs) for the associations between adolescent pregnancies and adverse birth outcomes with the 20-34 years age group as the reference. Separate multivariable logistic regression models were generated for preterm birth, LBW, ENND, each major birth defect category (neural tube defects, malformations of the eyes and ears, orofacial clefts, and malformations of the musculoskeletal system), and each of the 16 speci c birth defects. The analysis of preterm birth was limited to live births; while that of LBW and ENND was limited to term live births. The following covariates were considered for adjustment: parity, mode of delivery, singleton/multiple delivery, number of antenatal visits, and initiation time of prenatal care. The speci c covariates used in each model were selected based on previous studies, [6,[15][16][17][18] and excluded possible collider variables.
Birth prevalence per 10,000 births for seven categories of major external birth defects and 16 speci c birth defects [14] was calculated by maternal age group along with 95% Wilson's CIs.

Results
A total of 96,938 pregnancies with 100,189 births among mothers 12 to 34 years of age were captured. Of these, 11,028 (11.1%) births were among adolescent mothers and 89,161 (89.0%) births were among older mothers. Table 1 shows the maternal and infant characteristics by age group. The proportion of mothers with HIV infection was signi cantly lower in adolescent mothers (p<0.001) but a signi cantly higher proportion of HIV-infected adolescents had not initiated on antiretroviral therapy (ART) by the time of delivery compared to older mothers (p<0.001). Adolescent mothers were less likely to have attended any antenatal care (ANC), attended the recommended four or more antenatal visits, [19] or attended the rst antenatal visit within the rst trimester (p<0.001) compared to older mothers. Also, adolescents were more likely to have been referred from another health center for delivery, contributing 70% of referred women. Adolescent mothers were also more likely than older mothers to be primipara, have vaginal deliveries, and have singleton deliveries (p<0.001).

Discussion
In this study, we observed that adolescent mothers were more likely to have an infant with the adverse birth outcome of preterm delivery, LBW, ENND, or a major external birth defect such as gastroschisis as compared to older mothers. Previous studies have also found an increased risk for preterm delivery in adolescent pregnancies, [6,13,15] which could be attributable to the maternal-fetal competition for nutrients that arises when pregnancy coincides with continuing or incomplete growth in adolescents. [20] Our study nds that adolescent mothers were more likely to deliver LBW babies is consistent with results from the Uganda Demographic Health Survey 2011. [21] That survey also identi ed infants born with LBW to be at increased risk of neonatal death, [22] highlighting the risks associated with LBW in this population. The LBW observed among infants born to adolescent mothers could have been due to factors such as inadequate maternal nutrition, or the related but distinct issue of inadequate weight gain during pregnancy, [16] which were not assessed in our study.
Comparable to ndings from a study exploring the impact of early motherhood on neonatal mortality in 45 low and middle-income countries, our study showed that ENNDs in full-term babies occurred more frequently among adolescent mothers. [7] In contrast, a World Health Organization (WHO) multi-country survey across 29 countries in Africa, Asia, Latin America, and the Middle East found that ENND among infants born to adolescent mothers was not signi cantly different from mothers aged 20-24 years, after controlling for confounders. [6] This difference may be related to restriction in the WHO study to mothers aged 24 years or younger who gave birth to an infant of at least 22 weeks' gestation as compared to mothers ≤ 34 years in our analysis and the WHO study's classi cation of ENND as intra-hospital deaths that occurred within 7 days after birth as compared to deaths within 48 hours in our analysis.
In this study, adolescent mothers were more likely to deliver a newborn with a birth defect when compared with older mothers. These ndings are consistent with ndings from studies in North America and Europe. [23,24] Our ndings of a higher birth defects prevalence estimate (per 10,000 births) among adolescent mothers compared to older mothers is consistent with ndings from a population-based prevalence study using data from EUROCAT congenital anomaly registers in 23 regions of Although the number for some birth defects were small in our study, our ndings suggest that gastroschisis was signi cantly higher among adolescent mothers when compared to older mothers, as reported by other studies. [23,24,26] While comparing gastroschisis to other congenital anomalies, Given, et al. (2017) reported sexually transmitted infections, and continuation of oral contraceptives in early pregnancy, as preventable risk factors. [27] We were not able to assess these factors in this study. Our study also found that adolescent mothers were associated with increased odds of musculoskeletal defects as well as malformations of eyes and ears combined. Chen, et al. (2007) found increased odds of musculoskeletal defects, however, he included some other defects within the category, speci cally, polydactyly/syndactyly/adactyly, diaphragmatic hernia, integumentary anomalies. [23] We found that a signi cantly higher proportion of HIV-infected adolescents were not on ART at conception or delivery compared to older women, which is consistent with ndings from the Uganda Population-Based HIV Impact Household-based National Survey. [28] Maternal HIV infection has been shown to be associated with increased rates of adverse pregnancy outcomes such as LBW, prematurity, and ENND [29], and the lower prevalence of ART use among HIV-infected adolescents would further exacerbate the situation because it translates to a potential increased risk of MTCT of HIV among adolescents compared to older mothers justifying the need to strengthen services for this population. [30] Study Strengths This study's strengths include a large sample size, which made it possible to assess the association between adolescent pregnancy and possible risk factors of adverse birth outcomes. In addition, our study used an active birth defects case ascertainment and collection of data to ensure accuracy and improved birth defect detection and reporting versus extraction of data from medical records. Also, the physical examination of newborns by trained staff and several levels of external birth defect review ensured consistent birth defect classi cation and coding.
Unlike other studies that only include live births, [23,25] this study included stillbirths, spontaneous abortions, and live births which minimized selection bias especially since some structural birth defects commonly occur among stillbirths thereby giving more accurate risks and birth prevalence estimates among the different age groups.

Study Limitations
Study limitations include surveillance activities being conducted at four major urban hospitals located in the capital city and is not representative of adolescent pregnancies nationally. [5] Secondly, because infants were not followed post-discharge, we captured only ENND that occurred within 48 hours of birth. The standard de nition of ENND is death within seven days of delivery so infants that died between discharge and seven days of life was not accounted for, resulting in a possible underestimation of ENND.
Finally, this study did not control for several risk factors known to in uence reproductive health outcomes such as social-economic status, level of education, tobacco smoking, alcohol drinking, maternal nutrition, and the use of folic acid since this information was not captured in the surveillance. [18,31]

Conclusion
Our study is one of the few studies reporting adverse birth outcomes among adolescent women in sub-Saharan Africa. [32] Our results corroborate previous ndings in developed countries on birth outcomes and demonstrate that adolescent pregnancy is a risk factor for several neonatal adverse birth outcomes. With the growing population and high rates of adolescent pregnancy in Africa, the number of adverse birth outcomes is likely to increase and thereby remain a key public health concern. [5] Further research on individual, socio-cultural, environmental, economic, and health service-related factors are required to identify practicable and scalable measures to decrease adolescent pregnancy and to identify and reduce obstacles that discourage the use of quali ed antenatal services, that would prevent or reduce adverse reproductive outcomes such as neonatal deaths, low birth weight, birth defects, and mother to child transmission of HIV. The establishment of dedicated adolescent-friendly antenatal care programs would help improve neonatal and adolescent health, [33] and, better understand associated risk factors and the impact of younger maternal age on pregnancy outcomes. It is critical to monitor trends in birth outcomes and prevalence of major external birth defects across age groups to inform health-care policies and to plan for needed services among the affected population. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent pregnancies is necessary to identify possible interventions. Consent to participate in the surveillance was waived by both IRBs (JCRC and CDC) because the surveillance involves no more than minimal risk to the participants. However, IRB-approved written informed consent was obtained for photographs of newborns with birth defects from their mothers or legal guardians.   Early neonatal death model was restricted to full-term infants (gestation ≥37 weeks) and adjusted for parity, mode of delivery and number of antenatal visits.
Birth weight model was restricted to full-term infants (gestation ≥37 weeks) and adjusted for parity, mode of delivery, singleton/multiple deliveries and number of antenatal visits.
Overall birth defect model was adjusted for parity, mode of delivery, singleton/multiple births and number of antenatal visits. ¥ Newborns with at least one of the sixteen major external birth defects of interest to the study