Adverse Obstetric Outcomes at Advanced Maternal Age in Arba Minch Zuria, and Gacho Baba District, Southern Ethiopia: A Prospective Cohort Study

Background: Advanced maternal age signicantly increased the risk of adverse obstetric outcomes. So, adequate and updated information on the status of advanced maternal age and their effect on obstetric outcomes is vital for effective policy and program formulation in Ethiopia. Pockets of studies conducted, but most are retrospective and record reviews. Thus, studies that show the status of advanced maternal age and their effect on obstetric outcomes is very limited in Ethiopia. As such, this study lls those gaps in our set up. Methods: A community-based prospective cohort study was conducted among 709 study participants from October 15, 2018, to September 30, 2019. A pretested interviewer-administered structured Open Data Kit survey tool was used to collect the data. The downloaded data from the Open Data Kit aggregate was exported to SPSS version 25 for analysis. Log-linear regression was used to compare obstetric outcomes among women aged 20–34 years and ≥ 35 years. The model was adjusted for educational and occupational status, party, wealth index, body mass index, household food insecurity, habits, distance to health care institution, and sex of the neonate, antenatal care, postnatal care, and place of delivery. The model tness was tested by the log-likelihood ratio. Results: In this study, 209(29.5%) of the women were aged ≥ 35 years, and 500(70.5%) aged 20– 34 years. Women aged ≥ 35 years were at increased risk of miscarriage (β = 0.29, 95%CI: 0.02, 0.56), and hypertensive disorder (β = 0.07, 95%CI: 0.004, 0.13). Conclusions: Advanced maternal age was independently associated with miscarriage and hypertensive disorder after controlling for possible cofounders. As such, different intervention programs should be designed to create awareness and to provide counseling services for women with advanced age or delayed childbearing.

This study found that advanced maternal age increased risk of miscarriage (termination of pregnancy before fetal viability) and hypertensive disorder during pregnancy, the intrapartum and immediate postpartum period after controlled for possible confounders.
In brief, this study showed that a signi cant number of women became pregnant during advanced maternal age. Therefore, different strategies should be designed for the women who planned to bear child, and information should be provided for women who are advanced age or delayed childbearing to alert them.

Background
Advanced maternal age de ned as a mother bearing a child at the age of 35 or older. If women have a baby at this age, there are some risks comes for mom and baby. Despite this, more and more women are waiting until later in life to have kids [1][2][3].
Worldwide, nowadays delayed childbearing is a growing option, and this trend is stronger in developed countries [4][5][6]. The average age at childbirth in the UK is increasing, and more women are giving birth over the age of 35 years. In 2013, 20% of live births were to women over the age of 35 years [7]. In the last four decades, the rate of pregnancy in older women has increased [8]. Different studies which were conducted in Iran, Jerusalem, Israel; multi-country study; Norway; Asia; Muar district, Johor, Malaysia, Northeastern Brazilian city and cohort study in Israel showed that the incidence of pregnant women with advanced maternal age was 49.8%, 14%, 12.3%, 33.4%, 11.4-19.1%, 14.8%, 5.9% and 2.3% respectively [4,[9][10][11][12][13][14]. Similarly, other studies reported 4.53% from Nepal, 17.5% from South Africa, and 19.1% from the UK by North Western Perinatal Survey; which was a large contemporary cohort study [15][16][17].
The main reason for delayed childbearing is the effective use of family planning, rise in educational involvement of women, increased labor market participation, gender equity, housing conditions, and lack of family support police [18]. Besides, advances in economic, technological, and social changes have signi cantly contributed to the delayed bearing to their late 30 s and beyond. This huge demographic shift has become the main public health issue, and it becomes challenging for both patients and clinicians because delaying pregnancy too advanced age-related to the adverse obstetric outcomes [4,6,7,14,[19][20][21].
Various studies have been carried out to identify and assess the complications of pregnancy with increasing maternal age [16]. As maternal age advances, the risk of adverse obstetric outcomes elevated consistently [17,20,22]. The risk of maternal near-miss, maternal death and severe maternal outcomes signi cantly increased among women with advanced age [1,2,5,[9][10][11][23][24][25]. Women of advanced age had increased incidence of hypertensive disorder of pregnancy, and breech presentation as shown in studies conducted in Nepal, Cameroon, and South Africa [15,16,24]. The rates of operative vaginal delivery in women aged < 35, 35-39, and forty or more were 23.5%, 36.9%, and 43% respectively [7]. The rate of the cesarean mode of delivery increased threefold among women aged 35-40 and vefold among women over 40 years as compared to women aged ≤ 35 years old [4].
Thus, pocket studies conducted in parts of the different countries [1,2,5,[9][10][11][23][24][25], but most are retrospective and used secondary data sources or record reviews. Besides, there are very limited studies that show the effect of advanced maternal age on obstetric outcomes as delayed childbearing increases in-country Ethiopia. Consequently, adequate and update information on the status of advanced maternal age and there effect on obstetric outcomes are very important for effective policy and program formulation. Therefore, this study was aimed to assess the effect of advanced maternal age on obstetric outcomes in the study setting.

Inclusion criteria
At enrollment for this study, all women who were pregnant and inhabitants to a minimum of six months in the study area were eligible for this study. The eligibility was de ned by the pregnancy screening checklist which was developed by Whiteman et al. [26].

Exclusion criteria
During recruitment, all women whose ages less than twenty years old and known to be preexisting illnesses were excluded.

Sample size determination
The separate sample size was calculated in Epi info7 software Stat Calc for each speci c objective. To determine the sample size for the rst objective (to assess the status of advanced maternal age among pregnant women in Arba Minch zuria, and Gacho Baba district, southern Ethiopia, 2018/9) single population proportion was used by the following assumption: P = 0.334 from the study conducted in Norway [11], 95% level of con dence and 5% margin of error. Based on this, the estimated sample size was 342. To determine the sample size for the second objective (to determine the effect of advanced maternal age on obstetric outcomes among pregnant women in Arba Minch zuria, and Gacho Baba district, southern Ethiopia, 2018/9) two-sample comparison proportion was used. The assumption was P 1 (age group 20-34) = 0.207 and P 2 (age group ≥ 35) = 0.124 in one of the obstetric outcome (anemia) in advanced maternal age from the study conducted in Malaysia [14], 95%CI, ratio 1:1, and Power = 80% and the sample size estimated by this assumption was 676. The sample size for this study was estimated by adding a non-response rate of 10% to the larger sample size (sample size of the second objective). Therefore, the calculated sample size for this study was 744.

Data collection tool
The data were collected using a pretested interviewer-administered structured Open Data Kit (ODK) survey tool. The tools were developed by reviewing different works of literature. The questionnaire for wealth index indicators was adapted from Ethiopian Demographic Health Survey (EDHS) 2016 [27] and included ownership of household assets and equipment, water supply, power supply, sanitary facility, residential homes, farmlands, and livestock ownership. The household food insecurity level was measured with Household Food Insecurity Access Scale (HFIAS), a structured, standardized, and validated tool that developed mainly by Food and Nutrition Technical Assistance (FANTA) [28]. The tool contains three main parts: Annex I (checklist to recruit the mothers to the study (background and pregnancy Information, and pregnancy screening checklist); Annex II (the tool to obtain baseline information); Annex III (tools for follow up survey to obtain obstetric outcomes) (Additional le 1).

Pretest
The tools were pretested in the Chencha district, which was out of study area to verify the appropriateness of the tool, and modi cations and amendments were taken accordingly before actual data collection.

Data collection procedures
The well-trained nine data collectors and three eld supervisors were prospectively identi ed obstetric outcomes among pregnant women during the study period. Intensive three days training gave for data collectors and supervisors separately regarding objectives of the study, and data collections ways. Data collectors discussed the information about the ODK survey tool and pregnancy screening checklists to identify pregnant women. As this was a community-based prospective follow-up study, data collected in different phases. In the rst phase: all the baseline information about the women was obtained and pregnancy status was checked by using a pregnancy-screening checklist. After identi ed whether women were advanced age or not and the data collectors have recruited the women into the cohort of the study. The data were collected by home-to-home visits. In the second phase: the women were followed during pregnancy up to the immediate postpartum period to identify the obstetric outcomes. In the community setting the data collectors frequently contacted women or any household members, surround health care institutions, and health extension workers during the follow-up period.

Measurements
The description and measurements of the outcome and some of the explanatory variables were stated in detail below (Table 1). Those ful lled the stated criteria were coded as "1", not were coded as "2" Cesarean mode of delivery Gave birth by the invasive procedure (incision is done on the abdomen, facia, and uterine wall.
Those ful lled the stated criteria were coded as "1", not were coded as "2" Hemorrhagic disorders Any excessive vaginal bleeding after 28 weeks of gestation, and in the postpartum period.
Those ful lled the stated criteria were coded as "1", not were coded as "2" Miscarriage Any termination of pregnancy for a non-medical reason before fetal viability (before 28 weeks of gestation) Encountered women were coded as "1", and not encountered were coded as "2" Prolonged labor The mother stayed for more than 12 hours in labor after active onset.
Encountered women were coded as "1", and not encountered were coded as "2" Premature rupture of membrane Rupture of membrane before 18 hours of the onset of labor.
Encountered women were coded as "1", and not encountered were coded as "2" Anemia Maternal hemoglobin (Hb) < 10 g/dl, and signs like dizziness, blurred vision, and con rmed by a health professional and informed for the mother.
Women this condition were coded as "1", and not encountered were coded as "2" Severe maternal morbidity Severe disease condition during pregnancy, delivery, and postpartum periods like heart failure, renal failure, shock, and amniotic uid embolism.
Women faced such type of conditions and treated as critical in the health care institution were coded as "1", and not were coded as "2" Exposure variable Variables Description Measurements Advanced maternal age Pregnant mother aged ≥ 35 years old [7].
Categorized into two groups and for the mother aged 20-34 years old coded as "1" and "2" for ≥ 35 years.

Data quality assurance
To ensure quality, experts translated questionnaires into the local language. A standard tool, which was commented by many experts, was used to collect the information. The data collectors and supervisors were trained to standardize and ensure consistency of data collection. The ODK survey tool that was very important to control the quality of data. The principal investigator and supervisors critically checked the data for completeness before uploaded to the ODK cloud server. Multiple imputation techniques were used for missed data that were not more than 20% of the needed information. Those study participants with inconsistent information were excluded from the nal analysis. To maintain quality, the data were properly coded and categorized.

Data analysis and processing
The collected data downloaded from ODK aggregate and then exported to SPSS version 25 for analysis. Univariate analysis done in relation to maternal age. Principal Component Analysis (PCA) used to determine wealth quintiles. Bivariate and multivariable analysis done by using log-linear regressions. The assumptions for log-linear regression checked, and the goodness of t-tested by the log-likelihood ratio (LR). All the variables with P ≤ 0.25 in the bivariate analysis included in the nal model of multivariate analysis to adjust the confounding effect, and the variables selected by the backward stepwise technique. The model adjusted for educational and occupational status, party, wealth index, body mass index, household food insecurity access scale, habits, distance to health care institution, and sex of the neonate, antenatal care, postnatal care, and place of delivery to control the possible confounding effect. A standard error greater than two considered as suggestive of the existence of multi co-linearity. A crude and adjusted log-linear regression analysis done for each outcome variable with maternal age to estimate the beta coe cient (β). A statistically association declared at P-value < 0.05. Then the information presented by using simple frequencies, summary measures, tables, and gures.

Results
The overall process of the study and response rate Of the respondents, 744 (100%) were interviewed in the baseline based on the calculated sample size.
During the follow-up period, 24 participants became lost to follow-ups, and 11 excluded from the analysis gave the response rate of 95.3%.
Socio-demographic and economic characteristics in relation to maternal age  Household food insecurity access scale in relation to maternal age Of the women, whose age was 20-34 years old, 325 (65.0%), and 71 (14.2%), and whose age 35 years old or more 144(68.9%), and 14(6.7%) were food secure, and severely food insecure respectively (Fig. 1).
The habit of the mother in relation to age Regarding habit of the mother, 20(4.0%), and 93 (18.6% participants had smoked and consumed alcoholcontaining beverages for the age group from 20-34 years, and 14(6.7%), and 40 (19.1%) for age category 35 years old or more respectively (Fig. 2).
After controlling for possible confounders, hypertensive disorder (pre-eclampsia and eclampsia syndrome, gestational, and chronic hypertension) signi cantly associated with advanced maternal age. This was congruent with studies conducted in Iran [29], Israel [21], and South Australia [30]. Similarly, as maternal age increased above 35 years old was signi cantly increased miscarriage. This nding was in line with the study conducted in a high-income developed country [31]. This is due to strong shreds of evidence those certain genetic risks highly evident as maternal age increases, the quality of egg compromised, and the decreased physical ability to stay pregnant.
Advanced maternal age was not signi cantly associated with cesarean mode of delivery as shown in this study. This was contradicted by different studies conducted in Iran [29], South Korea [20], Israel [21], Sweden [32], United Kingdom [17], South Australia [30], and a high-income developing country [31]. This may be a difference in the health care delivery system, socio-economic factors, and methodological variations.
Hemorrhagic disorders were not associated with advanced maternal age in the adjusted model. This was not in line with a study conducted in Israel [21]. Correspondingly, severe maternal morbidity was not associated with advanced maternal age. This was contrasting with the study conducted in Washington State, United States [33]. Other Obstetric outcomes such as prolonged labor, premature rupture of membrane, and anemia were not associated with advanced maternal age. This is due to variation in measurement, and socio-economic, and socio-cultural factors.
The implication of this study for public health is paramount. Women in advanced age are the risk population group for different adverse obstetric outcomes. Nowadays women delayed childbearing related to different conditions, such as delayed marriage, using family planning, education, and workload (occupation). During advanced maternal age, women may face unpreventable adverse obstetric outcomes even if the health care system is advanced. As such, studies on the effect of advanced maternal age on the adverse obstetric outcomes are very important to strengthen the intervention for women who planned to conceive. The nding of this study initiates different stakeholders in the health care system to design appropriate strategies and planning for the measurements taken at both in the health care institutions as well as in the community at large. This study becomes one input for health policymakers and program developers typical regarding maternal health in the health care delivery system.
The main strength of this study that the design was a community-based prospective follow up that gave a true measure of the effect of advanced maternal age on adverse obstetric outcomes as compared to other study designs except for interventional study. Standard and validated tools used to measure the pregnancy status, baseline assessment to maintain validity and reliability. The adequate sample size used for a study that resulted in high power and greater precision. Besides, it had a high response rate which 95.3% as per the nature of follow-up, and to accesses the obstetric outcomes.
The limitations of this were some of the medical words were di cult to translate to the local language exactly. Nevertheless, the help of local experts did maximum effort. Some values are di cult to set cut off points, and based on the maternal response as subjected to social desirability bias.

Conclusions
This study showed that a signi cant number of women became pregnant during advanced maternal age. Those adverse obstetric outcomes are unpredictable, and unpreventable in the majority of bases, but highly increased during advanced age. This study identi ed that miscarriage, and hypertensive disorder was signi cantly associated with advanced maternal age. As such, different intervention programs designed to create awareness, and to provide counseling services for women with advanced age or delayed childbearing. The respondents also informed that the information obtained from them treated with the utmost con dentiality.

Figure 1
Household food insecurity access scale in relation to maternal age for the study conducted in Arba Minch zuria, Gacho Baba district, southern Ethiopia, 2018/9 Figure 2 Habit in relation to maternal age for the study conducted in Arba Minch zuria, and Gacho Baba district, southern Ethiopia, 2018/9 Supplementary Files This is a list of supplementary les associated with this preprint. Click to download.