key: cord-0743760-xt83skia
authors: Kurian, Simi; Mathews, Manu; Divakaran, Binoo; Reshmi, V.P.; Ajith, S.
title: Impact of diabetes on the severity of COVID-19 infection in pregnant women - A single-center descriptive study
date: 2021-12-09
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2021.102362
sha: 25f305f90d0dd02687d759de7fab7a8dfbd9bca5
doc_id: 743760
cord_uid: xt83skia

BACKGROUND AND AIMS: Pregnant women have significant morbidity and mortality due to COVID-19 infection. Pregnancy and diabetes are known risk factors for severe COVID 19 infection. Understanding the interactions between COVID-19 and diabetes in pregnancy is crucial in developing appropriate therapeutic approaches. India, like many other countries, has a very high prevalence of diabetes and COVID-19 infected cases. Such studies are minimal worldwide and none from India to the best of our knowledge. MATERIALS AND METHODS: We did a retrospective cross-sectional study. 856 COVID-19 infected pregnant women were included in the study. We estimated the impact of diabetes on the severity of COVID-19 infected pregnant women and compared the outcomes with the non-diabetic group. RESULTS: Prevalence of diabetes in pregnancy in the present study was 15.43%(n = 132/856). Prevalence of diabetes in non-severe infection was 14%(n = 115/818), severe infection was 44.73%(n = 17/38), and in maternal deaths was 75% (n = 6/8). The age-adjusted odds ratio for diabetes for severe infection was 4.492 (95% CI = 2.277–8.865, p < 0.001). COVID-19 infected pregnant women with diabetes were at higher risk for Cesarean section (78.3%) and ICU admission for newborns (14.81%) CONCLUSION: Diabetes in pregnant women is strongly associated with the severity of COVID-19 infection. The prevalence of diabetes in pregnancy increases as the severity of COVID-19 infection increases. Diabetes is associated with more adverse outcomes in mothers and newborns. It is necessary to identify pregnant women with diabetes and prioritize them in public health interventions like vaccination.

In the rapid outbreak of COVID 19 all around the world, pregnant women, like other people, are infected with the virus. Physiological respiratory and nonrespiratory changes and immunological changes during pregnancy may predispose pregnant women to COVID 19 infection and worsen outcomes.

Morbidity and mortality in COVID 19 infection are increased by comorbidities like Diabetes. (1) India is placed second worldwide with at least 77 million people (aged 20-79yrs.) living with diabetes. (2) India is also having one of the highest prevalence of COVID -19 infected cases. (3) It is necessary to determine the impact of diabetes on the severity of COVID-19 infection in pregnant women to modify the therapeutic strategies and reduce maternal morbidity and mortality. The vulnerable groups in pregnant women should be identified and prioritized in public health interventions like vaccination which is currently low due to safety concerns.

There are many studies on the risk of severity of COVID-19 infection in the general population with diabetes. Understanding the interactions between these two diseases is crucial in developing appropriate therapeutic approaches.

However, to the best of our knowledge, there are very few studies worldwide and none from India to assess the impact of diabetes on the severity of COVID-19 infection in pregnant women. There is limited data on maternal and newborn outcomes of COVID -19 infected pregnant women with diabetes compared to those without diabetes. It was in this background that we conducted this study.

J o u r n a l P r e -p r o o f 2 Materials and methods

We did a retrospective cross-sectional study with the primary objective to estimate the association of diabetes and the severity of Covid-19 infection in pregnant women. The secondary objective was to compare maternal and newborn outcomes among COVID-19 infected pregnant women with and without diabetes mellitus.

After obtaining approval from the Institutional Ethics Committee, the study was registered with the Clinical Trials Registry-India under CTRI/2021/09/036831.

A waiver of written informed consent was obtained due to the rapid emergence and highly infectious nature of the disease and being a record-based study with anonymized data.

The study was conducted in a designated COVID-19 tertiary care hospital and teaching institute with 1300 beds in Kerala, India. The study period was one year, from 1 August 2020 to 31 July 2021. Pregnant women with laboratoryconfirmed COVID-19 infection by Rapid Antigen Test or RT-PCR on the nasal/throat swab sample done as per the World Health Organization guidance and admitted during the study period were included. Patients transferred to other centres during treatment or discharged against medical advice were excluded.

Data of patients were collected from the Hospital Medical Record section.

From the study population, those with diabetes were identified. Gestational diabetes was identified by the Oral Glucose Tolerance Test (after 75 grams of oral glucose 2-hour plasma glucose value > 140 mg %) as per DIPSI criteria (4) which is followed by our institution. Pre-gestational diabetes was identified from the history and old medical records. Severe COVID-19 infection, as per National Institute of health COVID-19 treatment guideline (5) , was defined as lab-confirmed COVID-19 infection with respiratory distress and J o u r n a l P r e -p r o o f SpO2 < 94% on room air or respiratory rate >30/minute. Asymptomatic/ symptomatic patients with SpO2 ≥ 94% and respiratory rate ≤ 30 / minute were considered non-severe infections. At SpO2 < 94%, the patient was placed in a higher treatment category by state treatment guidelines (6) ,and steroids and oxygen supplementation were indicated.

The estimated maternal outcomes were severity of COVID-19 infection (nonsevere /severe/death), antepartum complications like preeclampsia, preterm labor, mode of delivery (vaginal/cesarean), and postpartum complications.

Newborn outcomes included prematurity, birth weight, Newborn Intensive Care Unit admission, neonatal COVID-19 infection and neonatal death.

Data abstraction forms included socio-demographic details, clinical characteristics, obstetric/medical history, maternal and neonatal complications.

Data retrieved from the medical records were reviewed and double-checked.

The dataset for the study was frozen on 31 July 2021.

Continuous variables were described by mean ± standard deviation (SD) or median (interquartile range (IQR), considering the normality. Counts and percentages described categorical variables. For testing the association of factors with severity, the Chi-square test for association was used. Logistic regression analysis was done to find the risk factors of severity of COVID-19 infection. A p-value less than 0.05 was considered significant. The data were entered into MS Excel, and analysis was done using SPSS version 24. Age: A significantly higher proportion of subjects aged more than 35 years who were diabetic compared to those aged less than or equal to 35 years, using the Chi-square test.

Gestational age: A significantly higher percentage of those between 28 to 37 weeks of gestation had diabetes than the other two gestational age groups (using the Chi-square test).

Symptoms: A more significant proportion of symptomatic had diabetes compared to asymptomatic (using Chi-square test). Among the symptomatic (n =183), the most common symptom was fever (60%), followed by cough (48%) and breathlessness (17%).

The most common comorbidity, other than diabetes, was hypertension. Other comorbidities were bronchial asthma, hypothyroidism, structural heart diseases, hematological and immunological diseases.

Severe COVID-19 infection were seen in 38 patients (4.43%, n = 38/856) and non-severe in 818 patients (95.56%, n = 818/856) . There were eight maternal deaths during the study period, out of which six were diabetic. Figure 2 shows the prevalence of diabetes in COVID-19 infection of varying severity in pregnant women.

Prevalence of diabetes in non -severe infection was 14% (n=115/818), in severe infection was 44.73 %( n=17/38) ,and in maternal deaths was 75% (n=6/8).

The association of different risk factors with severity of infection is given in Table 2 3 Table 2a shows the association between diabetes and the severity of infection.

As given in Table 2a , the proportion of cases with severe infection was significantly higher among people with diabetes than non-diabetics (using the Chi-square test for association).

The proportion of pre-gestational diabetic cases with severe infection was significantly more than the proportion of gestational diabetes cases with severe infection (using Fisher's exact test), as shown in Table 2b .

The association of comorbidities like hypertension and bronchial asthma with the infection severity is given in Tables 2c and 2d, respectively. There were no cases with chronic kidney disease, chronic respiratory disease other than bronchial asthma, cardiovascular disease other than structural heart disease or active malignancy in the study group.

Association of age with the severity of infection is given in Eight patients with severe COVID-19 infection died. All were having COVID pneumonia, and one had a pulmonary embolism. Six of the deceased were diabetic, and three among them had pre-gestational diabetes.

The neonatal outcome is shown in table 4

New-borns born to mothers in the diabetic group were more frequently admitted to Neonatal ICU (14.81%) than the non-diabetic group (9.76%). The most frequent reasons for Neonatal ICU admissions were transient tachypnea of newborn followed by respiratory distress syndrome and neonatal jaundice requiring phototherapy. The rate of perinatal transmission was similar between newborns born to mothers in the diabetic and non -diabetic groups. There were no vaccinated females in the study group, as the COVID-19 vaccination drive for pregnant women was approved in our state only from July 2021 due to maternal and fetal safety concerns.

Prevalence of comorbidities other than diabetes, like hypertension, bronchial asthma, hypothyroidism, cardiovascular diseases, were low in the study group and showed no association with severity of infection statistically. This finding is consistent with studies from India that COVID-19 severity and mortality were significantly associated with the status of diabetes, and its risk may not be modified by the presence of hypertension (7) .

The prevalence of diabetes in pregnancy in the present study was 15.43 % ( n=132/856). The prevalence of Gestational diabetes mellitus in different parts of India was about 3.8%-17.9 % (8) , which is high compared to about 2-5% in the western population. Even when diabetic patients without other comorbidities were analyzed, the results remained the same-inflammatory and pro-coagulant factors were significantly higher in diabetic patients. (1) Pre gestational diabetes was more associated with severe COVID-19 infection in pregnancy than gestational diabetes in our study. This finding is consistent J o u r n a l P r e -p r o o f with other studies that show that Type 2 diabetes mellitus is more associated with a worse prognosis since hyperglycemia, in addition to the association with the formation of advanced glycation end products, results in oxidative stress and inflammatory process that can also favor viral replication. (16) Therefore, patients with diabetes in pregnancy deserve more intensive attention and should be closely monitored due to the risk of rapid deterioration.

There was a higher Cesarean section rate in the diabetic group, reflecting the higher rate of pregnancy complications in this group. Preeclampsia was also higher in the diabetic group. Studies from South India have shown that cesarean section and preeclampsia rates were significantly higher among women with gestational diabetes. (17)

At the time of exposure, Gestational age was more than 37 weeks in most women in our study because detection was more in these patients as they had undergone COVID-19 screening near term or when admitted to the labor ward. Six of the deceased (75%, n=6/8) were diabetic. The case fatality rate among diabetic pregnant women was 4.54 %( n=6/132).

One death occurred in the first half of the study period and seven deaths in the second half. More deaths in the second half was due to the second wave of the pandemic in India, caused by the Delta variant of the virus, which was more severe than the first wave.

More newborns in the diabetic group were admitted to the Neonatal ICU, suggesting that complications were more in this group.

One risk factor for morbidity and mortality in COVID-19 infection during the study period was the resource crunch at the peak of the second pandemic wave in many parts of India. But such overwhelming of health care system was less 

The level of glycemic control in patients with diabetes may influence the severity of disease in pregnant women (21) but was not analyzed in the study.

Obesity, a risk factor for severe COVID-19 infection, was not analyzed in the study due to logistic reasons.

Diabetes in pregnant women is strongly associated with the severity of COVID-19 infection. The prevalence of diabetes increases as the severity of COVID-19 infection increases. Diabetes is associated with more adverse maternal and neonatal outcomes. Pregnant women with diabetes were more symptomatic and also had a higher rate of Cesarean section.

A healthy lifestyle with a balanced diet and exercise will decrease the risk of gestational diabetes and is a good long term strategy against future pandemic waves. Awareness of the strong association of diabetes with adverse outcomes will help the public health system focus on pregnant women with diabetes and prioritize health intervention strategies like vaccination. J o u r n a l P r e -p r o o f

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