Prediction of clinical outcomes in women with placenta accreta spectrum using machine learning models: an international multicenter study.

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.

The increasing use of the WHO Safe Childbirth Checklist: lessons learned at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, Cameroon.

BACKGROUND: Safe childbirth remains a daunting challenge, particularly in low-middle income countries, where most pregnancy-related deaths occur. Cameroon's maternal mortality rate, estimated at 529 per 100,000 live births in 2017, is significantly high. The WHO Safe Childbirth Checklist (SCC) was designed to improve the quality of care provided to pregnant women during childbirth. The SCC was implemented at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital to improve the quality of care during childbirth. METHODS: This study was a retrospective study to determine the adoption rate of the SCC and its association with maternal (eclampsia, perineal tears, and postpartum haemorrhage) and neonatal (stillbirth, neonatal asphyxia and neonatal death) complications. Data were collected 6 months after the introduction of the SCC. Multivariate binary logistic regression was used to analyse the association between the use of the SCC and maternofoetal complications. RESULTS: Out of 1611 deliveries conducted, 1001 records were found, giving a retrieval rate of 62%. Twenty-five records were excluded. During the study period, the checklists were used in 828 of 976 clinical notes, with an adoption rate of 84.8% and a utilization rate of 93.9% at 6 months. Severe preeclampsia/eclampsia was associated with the non-use of the SCC (2.1 vs 5.4%, p = 0.041). Stillbirth, neonatal asphyxia, and neonatal death rates were not significantly different between the checklist and non-checklist groups. However, for all neonatal outcomes, the proportion of complications was lower when the checklist was used. CONCLUSION: The use of the SCC was associated with significantly reduced pregnancy complications, especially for reducing the rates of severe pre-eclampsia/eclampsia. The use of the SCC increased to 93.9% of all deliveries within 6 months. We advocate for the use of the WHO Safe Childbirth Checklist in maternity units.

The Pattern of Cervical Cancer according to HIV Status in Yaoundé, Cameroon.

OBJECTIVE: To analyze the epidemiological aspects of invasive cervical cancer according to HIV status. METHODS: This was an historical cohort study from January 2010 to April 2017 in three hospitals at the Yaoundé city Capital, Cameroon, after the National Ethics Committee' approval. We included invasive cervical cancers with documented HIV status. Odds ratios and 95% confidence interval were calculated to assess the association between the different variables and HIV status. Survival was analyzed using the Kaplan-Meier. The level of significance was set up at <5%. RESULTS: Among the overall 213 cervical cancer patients, 56 were HIV+ (24.67%). Factors associated with positive HIV status were age below 40 (OR: 2.03 (1.38-2.67)), celibacy (OR: 2.88 (1.58-4.17)), nonmenopausal status (OR: 2.56 (1.36-3.75)), low parity, primiparity (OR: 2.59 (1.43-3.74)), and for parity with 2-4 children (OR: 2.24 (1.35-3.12)). Concerning the HIV+ patients, tumor was diagnosed late (stages III-IV) (OR: 2.70 (1.43-5.08)), undifferentiated (grade III) (OR: 7.69 (5.80-9.57)), with low median survival (9.83 months vs. 20.10 months). CONCLUSION: HIV is frequent among cervical cancer patients. In the HIV+ patients, the diagnosis was made at the advanced stage, cells were poorly differentiated, and the prognosis was worse.

Prediction of success of uterus-preserving management in women with placenta accreta spectrum (CON-PAS score): A multicenter international study.

OBJECTIVE: To create a model for prediction of success of uterine-preserving procedures in women with placenta accreta spectrum (PAS). METHODS: PAS-ID is a multicenter study that included 11 centers from 9 countries. Women with PAS, who were managed between January 1, 2010 and December 31, 2019, were retrospectively included. Data were split into model development and validation cohorts, and a prediction model was created using logistic regression. Main outcome was success of uterine preservation. RESULTS: Out of 797 women with PAS, 587 were eligible. Uterus-preserving procedures were successful in 469 patients (79.9%). Number of previous cesarean sections (CS) was inversely associated with management success (adjusted odds ratio [aOR] 0.02, 95% confidence interval [CI] 0.001-3.63 with five previous CS). Other variables were complete placental invasion (aOR 0.14, 95% CI 0.05-0.43), type of CS incision (aOR 0.04, 95% CI 0.01-0.25 for classical incision), compression sutures (aOR 2.48, 95% CI 1.00-6.16), accreta type (aOR 3.76, 95% CI 1.13-12.53), incising away from placenta (aOR 5.09, 95% CI 1.52-16.97), and uterine resection (aOR 102.57, 95% CI 3.97-2652.74). CONCLUSION: The present study provides a prediction model for success of uterine preservation, which may assist preoperative and intraoperative decisions, and promote incorporation of uterine preservation procedures in comprehensive PAS protocols.

Exploring the effects of peri-partum ingestion of traditional medicine on maternal and foetal outcomes: a prospective cohort study.

OBJECTIVE: In Africa, 80% of women ingest traditional medicine (TM) during pregnancy. Although widely used in Cameroon, no study in has either demonstrated its safety or effectiveness. Hence, we sought to determine the effects of TM ingestions during the peri-partum period on maternal and foetal outcomes. A cohort study was conducted from January to April 2016 in two referral maternity departments of Cameroon. We consecutively enrolled all consenting parturients with gestational age above 28 weeks. We divided them into two groups; exposed and unexposed. The exposure studied was ingestion of TM within 72 h prior to delivery. Variables studied were socio-demographic characteristics, type and frequency of TM ingested and details of labour. RESULTS: We enrolled a total of 603 parturients of whom 147 in the exposed group and 456 in the non-exposed group. The most frequently used TM were honey and Triumfetta pentandra A. Ingestion of TM in the peri-paritum period was associated with intra-partum vaginal bleeding, dystocic labour, tachysystole and uterine atony. No adverse neonatal outcome was observed. Overall, these findings could help guide the direction of future research into the safety and potential benefits of peri-partum TM use, as well as serving as a preliminary reference for counselling.

Diagnostic ambiguity of aseptic necrobiosis of a uterine fibroid in a term pregnancy: a case report.

BACKGROUND: Uterine fibroids are the most common uterine tumours in females of reproductive age. During pregnancy, uterine fibroids may be complicated by aseptic necrobiosis. We herein report an ambiguous clinical presentation of uterine fibroids in pregnancy and discuss the diagnostic challenges encountered in our resource-constraint setting. CASE PRESENTATION: A term pregnant Cameroonian woman was admitted to our maternity unit with clinical findings suggestive of a strangulated umbilical hernia. She underwent an emergency caesarean section which fortuitously revealed aseptic necrobiosis of a uterine fibroid, managed within the same surgical intervention by myomectomy. Her post-operative course was uneventful. CONCLUSION: The authors highlight the need for a high index of suspicion by healthcare providers, as well as the need for a multidisciplinary approach for a favourable maternal and foetal outcome.

Risk factors for ectopic pregnancy in a population of Cameroonian women: A case-control study.

OBJECTIVE: To identify the risk factors for ectopic pregnancy (EP) in a population of Cameroonian women. SAMPLE AND METHODS: We performed a matched case-control study; 88 women with diagnosed EP (cases), and 176 women with first trimester intrauterine pregnancy (IUP) (controls), who underwent questionnaires. Odds Ratio (OR) and 95% confidence intervals (CIs) were calculated and adjusted for potential confounding factors via multivariate logistic regression analysis. RESULTS: Of the fifteen identified risk factors, 4 were independently associated with increased odds of EP: prior pelvic inflammatory disease (PID) (adjusted odds ratio [AOR] 13.18; 95% CI 6.19-27.42), followed by current use of levonorgestrel-only pills for emergency contraception (LNG-EC) (AOR 10.15; 95% CI 2.21-46.56), previous use of depot medroxyprogesterone acetate (DMPA) (AOR 3.01; 95% CI 1.04-8.69) and smoking at the time of conception (AOR 2.68; 95% CI 1.12-6.40). CONCLUSION: The present study confirms the wide variety of EP's risk factors. Moreover, some new findings including current use of LNG-EC, previous use of DMPA, smoking at the time of conception are noteworthy. Thus, in our limited resources country where prevention remains the cornerstone for reducing EP chances of occurrence, clinicians should do enough counselling, especially to women with known risk factors. The necessity to facilitate access to more equipment to enable early diagnosis of EP is very crucial and should be seriously considered, in order to reduce the burden of EP in Cameroonian women.

Risk factors for nuchal cord entanglement at delivery.

OBJECTIVE: To identify nuchal cord risk factors. METHODS: The present case-control study was carried out between December 2016 and April 2017 at two hospitals in Yaoundé, Cameroon. Singletons with a nuchal cord at delivery (case group) as well as the two neonates without a nuchal cord delivered immediately after each case (control group), all in cephalic presentation, were included. Undated pregnancies were excluded. The main variables studied were maternal age, parity, pregnancy duration at delivery, cord insertion site, cord length, delivery weight, and fetal sex. RESULTS: A nuchal cord was present in 121 (6.0%) of 2015 singletons. The final analysis included 114 and 228 neonates in the case and control groups, respectively, with similar maternal age, parity, pregnancy duration, and delivery weight. Significant independent risk factors for nuchal cord formation were a cord length of 70 cm or more (adjusted odds ratio [aOR] 19.10, 95% confidence interval [CI] 8.63-42.04), a pregnancy duration of more than 42 weeks (aOR 7.43, 95% CI 1.46-37.21), marginal cord insertion (aOR 2.90, 95% CI 1.11-9.35), and a male fetus (aOR 2.14, 95% CI 1.16-7.74). CONCLUSION: Marginal cord insertion and post-term pregnancy should be added to the list of known nuchal cord risk factors.

Maternal and neonatal outcomes of vaginal breech delivery for singleton term pregnancies in a carefully selected Cameroonian population: a cohort study.

BACKGROUND AND OBJECTIVES: Vaginal breech delivery (VBD) is known to be associated with more perinatal and maternal complications. Very few studies on the subject have been carried out in poor-resource settings. The aim of this study was to determine maternal and neonatal outcomes in carefully selected cases of VBD for singleton term pregnancies in a tertiary centre in Cameroon. DESIGN: A retrospective cohort study. SETTING: A tertiary hospital in Yaounde, Cameroon. PARTICIPANTS: Cases of VBD of newborns weighing 2500-3500 g were matched in a ratio of 1:4 to consecutive vaginal cephalic deliveries (VCDs) of newborns weighing 2500-3500 g over a 5-year period. Both groups were matched for maternal age and parity. We excluded cases of multiple gestations, footling breech, clinically inadequate maternal pelvis, preterm delivery, post-term pregnancies, fetal demise prior to the onset of labour, placenta praevia and fetal anomaly incompatible with vaginal delivery. OUTCOME MEASURES: Neonatal and maternal adverse outcomes of VBD observed till 6 weeks after delivery analysed using Bonferroni correction. RESULTS: Fifty-three (53) VBDs were matched against 212 VCD. Unlike women who had VCD, those who underwent VBD were more likely to have prolonged labour (OR 8.05; 95% CI 3.00 to 11.47; P<0.001), and their newborns were more likely to suffer from birth asphyxia (OR 10.24; 95% CI 4.92 to 21.31; P<0.001). CONCLUSION: The study infers a strong association between VBD of singleton term pregnancies and maternofetal morbidity when specific protocols are applied. This, however, failed to translate into higher differences in perinatal mortality. This finding does not discount the role of VBD in low-income countries, but we emphasise the need for specific precautions like close monitoring of labour and adequate anticipation for neonatal resuscitation in order to reduce these complications.

Uterus preserving surgery versus hysterectomy in the treatment of refractory postpartum haemorrhage in two tertiary maternity units in Cameroon: a cohort analysis of perioperative outcomes.

BACKGROUND: Little evidence exists on the efficacy and safety of the different surgical techniques used in the treatment of postpartum haemorrhage (PPH). We aimed to compare uterus preserving surgery (UPS) versus hysterectomy for refractory PPH in terms of perioperative outcomes in a sub-Saharan African country with a known high maternal mortality ratio due to PPH. METHODS: This was a retrospective cohort study comparing the perioperative outcomes of all women managed by UPS (defined as surgical interventions geared at achieving haemostasis while conserving the uterus) versus hysterectomy (defined as surgical resection of the uterus to achieve haemostasis) for PPH refractory to standard medical management in two tertiary hospitals in Cameroon from January 2004 to December 2014. We excluded patients who underwent hysterectomy after failure of UPS. Comparison was done using the Chi-square test or Fisher exact test where appropriate. Bonferroni adjustment of the p-value was performed in order to reduce the chance of obtaining false-positive results. RESULTS: We included 24 cases of UPS against 36 cases of hysterectomy. The indications of surgery were dominated by uterine rupture and uterine atony in both groups. Types of UPS performed were seven bilateral hypogastric artery ligations, seven hysterorraphies, six bilateral uterine artery ligations, three B-Lynch sutures and one Tsirulnikov triple ligation with an overall uterine salvage rate of 83.3%. Types of hysterectomies were 26 subtotal hysterectomies and 10 total hysterectomies. UPS was associated with maternal deaths (RR: 2.3; 95% CI: 1.38-3.93.; p: 0.0015) and postoperative infections (RR: 1.96; 95% CI: 1.1-3.49; p: 0.0215). The association of UPS with maternal death was not attenuated after Bonferroni correction. Hysterectomy had no statistically significant adverse outcome. CONCLUSION: Hysterectomy is safer than UPS in the management of intractable PPH in our setting. The choice of UPS as first-line surgical management of PPH in resource-limited settings should entail diligent anticipation of these adverse maternal outcomes in order to lessen the perioperative burden of PPH.

A case report of bicornis bicollis uterus with unilateral cervical atresia: an unusual aetiology of chronic debilitating pelvic pain in a Cameroonian teenager.

BACKGROUND: Congenital uterine anomalies like bicornis or bicornuate uterus are relatively rare in sub-Saharan Africa. They are associated with an increased rate of spontaneous abortion, preterm delivery, and infertility. The occurrence of bicornis bicollis uterus with unilateral cervical atresia is exceptional and its management is controversial. We hereby report a rare cause of chronic pelvic pain in a Cameroonian teenager due to unilateral obstructive hematometra and hematosalpinx in the non-communicating horn of a bicornis bicollis uterus. CASE PRESENTATION: A 13-year-old premenarchal non-virgin female presented with chronic and severe cyclical crampy pelvic pain. On clinical examination, she had a perforated hymen, a single vagina, and one uterine cervix. A two-dimensional pelvic ultrasonography revealed hematometra but missed out the underlying anomaly. Failure to drain the hematometra by serial cervical dilatations prompted an exploratory laparotomy which revealed: bicornis bicollis uterus with a right rudimentary uterine horn communicating with the vagina and a left non-communicating uterine horn distended by hematometra due to a homolateral cervical atresia. She underwent utero-vaginal canalization and a left hemi-hysterotomy with drainage of the hematometra. The postoperative period was uneventful. Regular cyclic menses occurred thereafter beginning at the first postoperative month. She had complete resolution of symptoms without recurrence after six months. CONCLUSION: Due to the risk of compromised fertility from bicornis uterus and the diagnostic challenges akin to resource-limited settings, we highlight the need for a high index of suspicion by healthcare providers when faced with chronic pelvic pain in premenarchal adolescents.

Evaluation of patients' satisfaction after laparoscopic surgery in a tertiary hospital in Cameroon (Africa).

INTRODUCTION: Access to laparoscopy is low in Cameroon where customers' satisfaction has not been reported so far. We assessed patients' satisfaction with the process of care during laparoscopic surgery in a new tertiary hospital. METHODS: A questionnaire was addressed to consenting patients (guardians for patients under 18) with complete medical records who underwent laparoscopy at the Douala Gynaeco-Obstetric and Paediatric Hospital (Cameroon) from November 1, 2015 to July 31, 2016. The following modified Likert's scale was used to assess satisfaction: very weak: 0-2.5; weak 2.6-5; good: 5.1-7.5; very good: 7.6-10. Only descriptive statistics were used. RESULTS: Response rate was 90% (45/50). Of the 45 respondents, 39 (86.7%) were female, 14(31.1%) were referred and 39 (86.7%) paid by direct cash deposit. Mean age was 36.8±11.9 years. Laparoscopies were carried out in emergency for 3 (6.7%) patients. Digestive abnormalities indicated 13 (28.9%) laparoscopies while gynaecologic diseases accounted for 32 (71.1%) cases. Perception of the overall care process was good with a mean satisfaction score of 6.8 ± 1.4. Scores in categories were: 0% (Very weak); 13.3% (weak); 57.8% (good) and 28.9% (very good). Specifically mean satisfaction scores were: 7.8 ± 1.0 with doctors' care; 7.1 ± 1.3 with hospital administration; 7.0 ± 1.2 with nursing and 4.7 ± 1.4 with the costs. Main complaints were: long waiting time (73.3%), constraining geographical access (66.7%) and expensiveness (48.9%). CONCLUSION: Patients were globally satisfied with the process of care but financial and geographical barriers should be addressed.

Etiologies de la mortalite maternelle a l'hopital gyneco-obstetrique et pediatrique de Yaounde: une serie de 58 deces

Objectifs: L'objectif de ce travail etait d'analyser les etiologies des deces maternels survenant dans un hopital de niveau tertiaire. Methodologie: Il s'agit d'une etude transversale avec collecte des donnees retrolective des deces maternels ayant eu lieu a l'Hopital Gyneco-Obstetrique et Pediatrique de Yaounde du 1er Janvier 2007 au 31 Decembre 2010. Tous les cas de deces maternels conformes a la definition de l'Organisation Mondiale de la Sante ont ete inclus. Les donnees ont ete analysees par les logiciels informatiques Epi info 3.5.1 et Excel 2007. Resultats: Cinquante-huit (58) deces maternels ont ete identifies pendant la periode de l'etude. Les principales causes de mortalite maternelle etaient : l'hypertension (22;4%); le VIH/SIDA (19;0%); les avortements septiques (17;2%); les hemorragies (13;8%); les cancers (10;3%) et la septicemie du post-partum (8;6%). Conclusion: L'hypertension; le VIH; et les avortements septiques sont les principales causes de mortalite dans cet hopital de niveau tertiaire. Les hemorragies ne sont responsables que d'une faible proportion des deces maternels. Nous recommandons la mise en place d'interventions visant a prevenir les deces maternels dus a l'hypertension en grossesse; a l'infection au VIH et aux avortements septiques. D'autre part; une politique hospitaliere basee sur la mise a disposition; sans frais exigibles en urgence; des paquets minimum pour les interventions obstetricales; de poches de sang et des equipes chirurgicales et anesthesiques; pourrait reduire efficacement la part des hemorragies dans la survenue des deces maternels en Afrique subsaharienne

Sexual activity of adolescent school girls in an urban secondary school in cameroon.

BACKGROUND: The objective of this study was to describe the extent of sexual activity in adolescent school girls. METHODS: This was a cross-sectional study with prolective collection of data carried out at Lycée General Leclerc, Yaounde (Cameroon), from October 1 to November 30, 2011. Heterosexual coitus was considered as sexual activity. A pretested self-administered questionnaire was proposed to all consenting girl students aged 10 to 19 years. The data were analyzed using Epi Info 3.2.1 and Microsoft Excel 2007 software. RESULTS: Of the 2660 students who responded to the questionnaire, 21.3% (566) admitted being sexually active. Out of these, 64.3% (364) were aged between 10 and 16 years at their first heterosexual contact. The mean age at the first sexual intercourse was 15.3 years. Although 56.4% (319) of the sexually active respondents had only one sexual partner, 43.6% (247) of them had at least two partners. Sexual activity was occasional in 71.4% of those being sexually active. Meanwhile, 52.1% (295) of the sexually active adolescent girls used condoms during sexual intercourse, 41.5% (235) did so occasionally, and 6.4% (36) had regular unprotected sex. CONCLUSION: More than one-fifth of adolescent girls were sexually active in this study. Sexual intercourse started mostly at the age of 16 or less, and it was mostly occasional. Half of the cases had multiple sexual partners, and half were not using condoms during sexual intercourse. We, thus, recommend the implementation of interventions aimed at delaying the age of the first sexual intercourse and accessibility of condoms to students in this setting.

The diagnosis of uterine cervical polyps in a low resource setting: the positive predictive value of clinical judgment--a series of 192 cases at the Yaounde Gynaeco-Obstetric and Paediatric Hospital, Cameroon.

As far as we know, the accuracy of clinical judgment in diagnosing uterine cervical polyps has not been assessed in sub-Saharan Africa. Our objective was to discover the positive predictive value (PPV) of clinical judgment in the diagnosis of cervical polyps. This is a retrospective descriptive study of 192 patients, carried out by the Departments of Pathology and Gynaecology of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, Cameroon. The diagnosis of cervical polyp was confirmed by histopathology examination in 169 patients, giving a PPV rate of 88.0%. The PPV of clinical judgment in the diagnosis of cervical polyps is acceptable in our setting but the frequency of premalignant and malignant lesions encountered is too high (10.4%), even in the presence of a confirmed cervical polyp (8.9%). Even in areas where there are limited resources, we recommend a systematic histopathology examination of any clinically suspected cervical polyp.

Pregnancy outcome at advanced maternal age in a group of African women in two teaching Hospitals in Yaounde, Cameroon.

INTRODUCTION: Women older than 40 years have been termed "advanced maternal age" and considered to be at risk of adverse pregnancy outcome. This study aimed to examine the obstetrical outcomes among primiparous and multiparous African advanced maternal age women. METHODS: We conducted a retrospective cohort study study at two teaching hospitals at Yaounde, Cameroon. From the hospital records, obstetrical characteristics of 585 consecutive women aged 40 or above who delivered from January 2007 to December 2011 were compared with those of 1816 younger mothers aged 20 to 29 years as control cases. Associations between maternal age and selected obstetrical variables were assessed with the contigency X (2) test or two-tailed Fisher exact test. RESULTS: Primiparous and multiparous advanced maternal age were more likely to undergo cesarean delivery than were their younger counterparts (38.5% vs 13.5%, RR=2.85, p<0.05 and 16.1% vs 9.1%, RR=1.76, p<0.05). Older primiparous women had similar perinatal outcomes than their younger counterparts. Older multiparous women had increased incidence of preeclampsia/eclampsia (2.4% vs 0.6%, RR=4, p<0.01); antepartum hemorrhage (1.8% vs 0.8%, RR=2.25, p<0.01); fetal distress (3.5% vs 1.3%, RR=2.69, p<0.01); fetal death (3.5% vs 1.6%, RR= 2.18, p<0.05); postpartum hemorrhage (2.4% vs 1.2%; RR=2, p<0.05); preterm delivery (12% vs 9.2%, RR=1.30, p<0.05); low birth weight (11% vs 7.7%, RR=1.42, p<0.05); admission to special care neonatalogy unit(14.1% vs 10.2%, RR=1.38, p<0.05); low Apgar scores at 1min and 5min; and perinatal mortality (3.5% vs 1.6, RR=2.18, p<0.05). CONCLUSION: Advanced maternal age women are at higher risk to cesarean delivery. Increased risk of antepartum and intra partum complications among multiparous advanced maternal age women were associated to adverse perinatal outcome. Our results are in concordance with the view that increased risk of adverse perinatal outcome with advanced maternal age is indirectly related to age through the increased risk of obstetrical complications associated with age.