Coronavirus disease 2019 (COVID-19) is a novel acute respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] . The case of this disease was reported in Wuhan China in December 2019. This rapidly triggered a global health emergency alert, with the disease spreading to many countries resulting in its declaration as a pandemic by the World Health Organisation (WHO) on the 12^th of March 2020 [2] . Genomic sequencing of SARS-CoV-2 found that this virus is related to two other viruses: Severe acute respiratory syndrome coronavirus 1 (SARSCoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV) [3] . As of June 23, 2022 a total of 539,893,858 confirmed cases of COVID-19 including 6,324,112 deaths (occurring mostly in industrialised countries), 533,569,746 recoveries and a total of 11.9 billion vaccine doses administered worldwide have been recorded [1] . In Africa, 12,267,000 cases of COVID-19 have been confirmed, with about 255,000 reported deaths as of June 2022 [4] . In Cameroon, from January 3, 2020 to 23 June 2022, there had been 120,002 confirmed cases of COVID-19 with 1930 deaths reported and a total of 1.8 million doses of vaccine were administered [4] .

Earlier on, many questions had been raised regarding the effects of COVID-19 on pregnant women, including whether pregnancy increased susceptibility to SARSCoV-2 infections, or whether pregnant women were more likely to have severe infections or increased adverse pregnancy and neonatal outcomes. Described prevalence of COVID-19 among the obstetric population varies by region, testing period during the pandemic, and testing methodology. Early reports by the Centres for Disease Control and Prevention (CDC) stated that COVID-19 positivity in pregnancy ranged from <1% to 19.9% [5] . In a study carried out in 2020 in Douala, Cameroon, the prevalence of COVID-19 among pregnant women was 6%, representing 2.3% of all COVID-19 cases [6] .

A high-quality systematic review and meta-analysis in 2021 found increased risk of preeclampsia, preterm delivery, gestational diabetes, low birth weight and still birth amongst pregnant women infected with COVID-19 than in pregnant women who were not infected [7] [8] [9] [10] [11] . Increased caesarean section rates, hypertensive disorders of pregnancy, premature rupture of membranes, maternal mortality, prematurity, foetal distress, neonatal asphyxia, neonatal deaths, are also commonly reported adverse pregnancy outcomes [12] .

A retrospective study carried out in South Africa in 2021 on the clinical features and outcome of COVID-19 infection among pregnant women reported that; 53% of the women presented with COVID-19 related symptoms, with preterm labour, increased caesarean sections and maternal exhaustion as most common maternal outcome, while adverse foetal outcomes though less frequent, were represented mainly by fatal distress, prematurity, neonatal asphyxia, macerated still births, and neonatal deaths [13] .

In Cameroon, a study carried out in Douala titled: Materno-Foetal Outcomes of COVID-19 Infected Pregnant Women Managed at the Douala Gynaeco-Obstetric and Paediatric Hospital—Cameroon reported preterm labour, maternal respiratory distress, caesarean section deliveries as the most common adverse maternal outcome while prematurity and neonatal asphyxia were the most encountered adverse foetal outcome [6] . A similar study carried out in 2020 in Yaoundé for three months titled: Maternal and foetal outcomes of COVID-19 pregnant women followed up at a tertiary health unit found no significant association between the occurrence of severe COVID-19 pneumonia and unfavourable prognosis in pregnancy [14] .

Outcome of pregnancy among women infected with COVID-19 remain an area of ongoing research due in part to the imprecise nature of results published. Thus, more probing for knowledge in this vast area of research will improve anticipation and awareness of adverse pregnancy outcome and hence better preparedness to improve prognosis.

The ongoing COVID-19 pandemic has been declared to have a poorer prognosis among people with underlying comorbidities such as hypertension, diabetes, obesity and now immune depressed states such as pregnancy [14] . Knowledge lapses existing in our setting hinder the formulation of standard follow up procedures and protocols that may prevent adverse pregnancy outcomes related to COVID-19 infection.

To the best of our knowledge, a limited number of studies on COVID-19 have been published in Cameroon evaluating maternal and foetal outcome among COVID-19 infected pregnant women. The first study was a descriptive study carried out over a period of three months, with 56 % of the study population having an ongoing pregnancy and at the end of the study [14] . The second study was a descriptive-cross sectional study carried out over a period of 4 months with 27.7% of the study population having an ongoing pregnancy at the end of the study [6] .

The limited sample sizes and short duration of study in the above-mentioned studies creates a restrain on the generalizability of their conclusions. Moreover, lack of comparison groups in the existing studies makes it difficult to directly incriminate adverse pregnancy outcomes to COVID-19 infection. With the aim of overcoming some of this informative draw backs, this study titled—Maternal and foetal outcome among pregnant women infected with COVID-19 in three Referral Hospitals in Cameroon, was done with a two-year period using a control group.

1) What is the impact of COVID-19 infection on maternal health?

2) What is the impact of maternal COVID-19 infection on the foetus?

3) How does the outcome of pregnancy vary between COVID-19 infected pregnant women and the non-COVID-19 infected pregnant women?

This was a two-year hospital-based retrospective case control study.

The study was carried out at the Obstetrics and Gynaecology departments and departments for care of COVID-19 patients of some referral hospitals in Cameroon including; Yaoundé Central hospital, Bamenda Regional Hospital and the Douala Gynaecologic Obstetric and Paediatric Hospital.

Located in the Center Region in the Cite Vert’ Health district, the Messa Health Area, the Yaoundé Central Hospital serves as one of the referral and teaching hospitals in Cameroon. The Obstetrics and Gynaecology unit of this referral hospital is composed; two common delivery rooms, room for residents, common and individual in-patient wards with an average capacity of 95 beds, four outpatient consultation boxes for obstetricians, emergency and intensive care, a family planning unit, archive, a conference room, three theatres, and neonatology. The services offered here run 24/7 by a highly qualified staff composed of: A Professor of Obstetrics and Gynaecology, seven specialist obstetricians and gynaecologists, a multitude of interns and residents, two general practitioners nurses, medical students and other paramedical staff. The department for care of COVID-19 infected patients in the YCH was instituted in August 2020. It consists of 8 hospitalisation units each with a capacity of about 2 beds, an office for the ward charges and an office for the doctors’ consultation. Running of the service is under the supervision of the ward charge and two general practitioners but however being visited by several specialists in the hospital as need be.

Bamenda Regional Hospital. It is the biggest hospital in the Mezam Division of the Northwest Region of Cameroon. It is in the Azire Health Area of the Bamenda Health District. The study was carried out in the BRH maternity and the COVID-19 treatment centre of the hospital (solidarity ward), which is so far the only COVID-19 treatment centre in this Health district. The Solidarity Ward is composed of a single bloc with 23 hospitalization rooms and 25 beds used as follows: 21 isolation/hospitalization rooms containing a bed each and 2 rooms allocated for the ICU each containing 2 beds. The others (asymptomatic and mild cases) are on home quarantine or ambulatory treatment. Pure oxygen, oxygen concentrators and pulse oximeters among other essential resources are available within the centre, the staff in this unit are comprised of a general practitioner, nurses and cleaner, who are supervised by a specialist.

The Douala Gynaeco-Obstetric and Paediatric Hospital. It is one of the referral hospitals in Littoral region located at Yassa with a very high patient turnover, dispenses high quality medical care, serves as educational support and promotes research. This hospital has four hospitalisation units: obstetrics and gynaecology, medicine, surgery and paediatrics, well equipped laboratory and radiology units and specialist clinicians. Added to that, it has a highly technical platform with specialised units like neonatology and intensive care.

The Obstetrics and Gynaecology department comprises of a hospitalisation ward that contains eight rooms containing 3 to 6 beds each and four private rooms containing 1 to 3 beds repartitioned for patients with; normal delivery, gynaecological pathologies, obstetrical pathologies, operated patients, an outpatient ward with 6 consultation boxes, a theatre and a room for celioscopy, six gynaecologists, nurses and midwives.

We chose the above hospitals because they are the main hospitals that receive and manage COVID-19 cases in pregnancy and sample size will easily be attained.

Files of women who delivered in the above hospitals during the study period.

Data collected were initially entered into questionnaires by the principal investigator, and then into a Microsoft excel version 2016 data base created for this purpose. It was analysed using statistical package for social sciences (SPSS) for windows version 27. Frequency tables were used to summarize descriptive and categorical variables, while mean, median, standard deviation, and inter-quartile range were used to represent continuous variables and results reported as per objective. Chi squared test was used to calculate p-values, with statistical significance set at <0.05.

We recruited a total number of 204 files at the beginning of our study: 68 cases and 136 controls. 7 cases (10.29%) were excluded alongside their corresponding 14 controls due to either incomplete files (didn’t meet the inclusion criteria), ongoing pregnancy or inability to reach participant by phone call. We therefore retained 183 participants, 61 cases and 122 controls for analysis. All our cases were singleton pregnancies (Figure 1).

Maternal age in our study ranged from 19 - 42 years. Majority of cases were in the age range of 25 - 34 years (59%). Mean age of study participants was 30.02 ± 5.9 (19 - 41) for cases and 30.2 ± 6.1 (19 - 42). Most of our cases (59.0%) and controls (60.6%) were married. A proportion of our cases were government employed (29.5%) while majority of controls were self-employed (35.2%). A majority of our cases (41.0%) and controls (23.0%) had university degree (Table 1).

We got most of our cases from the Bamenda Regional Hospital (37.7%), followed by DGOPH (32.8%) and the least number of cases from the YCH (29.5%) (Figure 2).

Majority of our cases were multiparous (80.3%). Mean gestational age at presentation was 37.05 ± 5.3 (10 - 43). A majority of our cases, >70% presented in the third trimester of gestation.

68.9% of our cases and 73.8% of controls did not appropriately follow up their antenatal consultations according to the WHO recommendation. The number of antenatal clinics (ANCs) done is also shown on Table 2.

Hypertension had a highest odds ratio with a 95% confident interval 2.13 (0.51 - 8.84), followed by HIV, 1.50 (0.54 - 4.16) and diabetes mellitus 1.38 (0.22 - 8.50). However, there was no statistical significance (Table 3).

A majority of cases presented with fever (22.0%), cough (19.2%) and asthenia (14.1%). 4.9% of the cases were asymptomatic (Table 4).

Preterm delivery was statistically significant with a P value less than 0.05 with an OR 2.51 (1.12 - 5.63). Maternal mortality among cases was at 8.2% as compared to 6.6% in the controls with OR 1.60 (0.50 - 5.12), which was not statistically significant (Table 5).

Rate of caesarean section deliveries among our cases was 52.5% as compared to 44.3% in the controls with OR 1.38 (0.74 - 2.60), with P value no statistically significant at 0.296 (Table 6).

The most common indication for caesarean section in our cases was acute foetal distress 26.2% whereas the most common indication in the controls was previous scar 18.3%. There was a statistical significance with previous scar (P value < 0.05) while the rest of the caesarean section indications were not statistically significant (Table 7).

Perinatal death rate among cases was recorded at 8.2% as compared to 3.4% in the controls (OR, 2.63, 95% CI, 0.68 - 10.18) which was not statistically significant, P = 0.16 (Figure 3).

Majority of newborns in both cases and controls had a birth weight ranging from 2500 - 3900 g. There was no statistical significance recorded in birth weights (Table 8).

OR = Odds ratio, P = P value, CI = Confident interval, Statistical test for significance = Chi-square test.

Majority of neonates both in cases and controls had an APGAR score 0.56 (0.16 - 1.93). There was no statistical significance in APGAR scores (Table 9).

21 neonates were admitted into the neonatology unit giving an admission rate of 36.2%. The most common indication for neonatal admission was perinatal

asphyxia covering 19.7% 10.7% of all admissions in the cases and controls respectively (Table 10).

Maternal ages in our study population ranged from 19 - 42 years, with mean age of cases 30.02 ± 5.9 (19 - 41) years and mean age of controls 30.2 ± 6.1 with a greater majority within the range of 25 - 34 years (59%). Our results were similar to the study done by Dingom et al. in Yaounde (64%) [10] .

Mean gestational age at presentation in our study was 37.05 ± 5.3 with gestational age ranging from 10 - 43 weeks. Over 80% of cases presented in the third trimester, similar to Ngalame et al. [6] and Sutton D et al. [11] where majority of cases presented in the third trimester of gestation.

The highest comorbidity recorded in our study was HIV, 11.5% and 8.2% in cases and controls respectively. But hypertension had a higher odds ratio in a 95% confident interval 2.13 (0.51 - 8.84), followed by HIV, 1.50 (0.54 - 4.16) and diabetes mellitus 1.38 (0.22 - 8.50, implying that hypertension was the

comorbidity associated with the highest risk of disease severity in our study. In a case control study by Khalil et al. on impact of COVID-19 infection on pregnancy and neonates. A low rate of associated comorbidities could be explained by good access to health care services and small sample size [12] .

In our study, most cases presented with the following symptoms of COVID-19 at diagnosis: fever (22.0%), cough (19.2%) and asthenia (14.1%). This is similar to a study done in Douala by Ngalame et al. which also recorded fever (27.4%) and cough (21.5%) as the most common presenting symptoms. In several other studies, fever was the major presenting symptom [6] .

The rate of caesarean section among our cases was 52.4% as compared to 44.3% among the control group with an odds ratio of 1.38 (0.74 - 2.60) indicating a causal effect between COVID-19 in pregnancy and caesarean section deliveries. A similar rate of C/S deliveries (61.5%) was noted by Ngalame et al. in a prospective study in Douala [6] . However higher rates of caesarean section were noted in COVID-19 infected pregnant women out of our context as the 83.5% obtained by studies carried out in [6] Thompson et al. (70% - 84.7%) [8] , Wei et al. (94%) [7] . The higher rates of caesarean sections in these studies is explained by the fact that non obstetrical indications were considered due to considerations that maternal respiratory distress would be improved by expeditious delivery.

Caesarean sections were mostly indicated for foetal distress 27.6% with odds ratio of 2.01 (0.94 - 4.27) and P value statistically significant at 0.044. This is similar to the results obtained by Sutton et al. where caesarean section in COVID-19 infected women was mostly indicated for foetal distress [11] .

We recorded higher rates of vaginal delivery (44.8%) as compared to other studies, 6% as obtained in [7] , and 18.8% as obtained in [8] . The rates of vaginal delivery where however higher in the control groups (53.8) with OR of 0.70 (0.37 - 1.31).

There was a 3.3% increase in spontaneous abortion in the cases as compared to the controls, with OR of 10.29 (0.49 - 2.17) indicating a 10 times increase risk of spontaneous abortion from COVID-19 infection in early pregnancy, which was however not statistically significant, P value = 0.106. Higher rates were recorded by Dingom et al. 12.5% [10] . Lower rates in our study can be explained by the fact that a higher proportion of our study population presented in the third trimester.

Maternal mortality rates in our cases were at 8.2% which was not statistically significant with a P value of 0.42. Maternal mortality rates were however lower in the control group (6.6%) with an OR 1.60 (0.50 - 5.12) indicating a more than 1.5 times increased risk of maternal mortality from COVID-19 infection in pregnancy. Lower rates were recorded in a meta-analysis by Ngalame et al., 1.4% and in the study carried out in which recorded 1.7%.

The rate of preterm delivery in our study was 24.6%. This was statistically significant with a P value 0.025 our results were closely similar to a study done by Thompson et al. with preterm delivery rates at 15.2% - 20.1% [8] . Ngalame et al. 29.7% [6] , Dingom et al. 21.2% [10] and Wei et al. 17% [7] . The rates where however lower (11.5%) in the control group with an OR 2.39 (1.05 - 5.42) signifying that pregnant women infected with COVID-19 had a double risk of preterm deliveries as compared to pregnant women not infected with COVID-19, similar to what was found in a case control study on maternal and neonatal outcome of pregnancy in women with COVID-19 by Taubenberger et al., with preterm delivery, significantly higher in cases than in the control group [15] .

Perinatal asphyxia was the highest reason for admission of neonates born to COVID-19 infected women into the neonatology unit (19.7%), followed by neonatal infection (6.6%), low birth weight (4.9%). With similar trends noted in the control groups. All admission indications were not statistically significant, all P values greater than 0.05. Perinatal asphyxia among the case and control groups produced a P value of 1.66 (0.43 - 6.38) indicating a causal effect between COVID- 19 infection in pregnancy and perinatal asphyxia.

Perinatal death rates in our study were recorded at 8.2% as compared to 3.4% in the controls with OR 2.63 (0.68 - 10.18) indicating a double risk of perinatal mortality in COVID-19 infection, which was however not statistically significant, P value = 0.16.