Gestational diabetes mellitus and COVID-19, clinical characteristics and review of the literature

  • Jorge R. Violante-Cumpa
    Affiliations
    Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Madero and Gonzalitos Av. s/n Col. Mitras Centro, Monterrey, Nuevo León, 64460, Mexico
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  • Fernando J. Lavalle-González
    Correspondence
    Corresponding author.
    Affiliations
    Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Madero and Gonzalitos Av. s/n Col. Mitras Centro, Monterrey, Nuevo León, 64460, Mexico
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  • Leonardo G. Mancillas-Adame
    Affiliations
    Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Madero and Gonzalitos Av. s/n Col. Mitras Centro, Monterrey, Nuevo León, 64460, Mexico
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  • Edmundo D. Ávila-Hipólito
    Affiliations
    Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Madero and Gonzalitos Av. s/n Col. Mitras Centro, Monterrey, Nuevo León, 64460, Mexico
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  • Karla A. Violante-Cumpa
    Affiliations
    Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Madero and Gonzalitos Av. s/n Col. Mitras Centro, Monterrey, Nuevo León, 64460, Mexico
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Published:August 02, 2021DOI:https://doi.org/10.1016/j.pcd.2021.07.016

      Highlights

      • GDM prevalence in women with COVID-19 is approximately 7.5–11.6%.
      • Cough was the most common clinical presentation of COVID-19 among women with GDM.
      • Maternal prognosis depends on mother’s age, comorbidities and severity of COVID-19.
      • Newborn prognosis is usually good but highly depends on maternal complications.

      Abstract

      There is a lack of information about the maternal-fetal outcomes in patients with gestational diabetes and concomitant COVID-19; and there is even less information about the outcomes of pregnant women with gestational diabetes and COVID-19. We present a case of a primigravidae of 20-year-old woman with gestational diabetes and COVID-19 and a review of the literature.

      Keywords

      1. Case report

      A 20-year-old woman was evaluated at a primary healthcare clinic with a complaint of a productive cough of 6-days evolution without dyspnea or fever. She was referred to our center because of hyperglycemia. The patient had a medical history of obesity (BMI of 31.6 kg/m2 at conception), and she was in her first pregnancy at 30 weeks of gestation with a diagnosis of gestational diabetes mellitus during her 27th week of pregnancy with a BMI of 34.8 kg/m2 at the time of her evaluation. Her serum glucose levels after a 75 g-OGTT were 107 mg/dl (baseline), 195 mg/dl (1 h) and 164 mg/dl (2 h). The patient is treated with NPH insulin 20 IU twice a day with poor adherence and no blood glucose self-monitoring for economic reasons. She has a poor understanding of her disease and lacks medical care due to the COVID-19 outbreak.
      During the interview, the patient denied a previous diagnosis of T2DM. At her first prenatal visit (6 weeks of gestation), she had a fasting glucose of 90 mg/dL with no further evaluations. On initial examination, her body weight was 87.3 kg, height 1.57 m, with a BMI of 35.4 kg/m2. Her vital signs were unremarkable, and she did not need supplemental oxygen; however, what was remarkable was acanthosis on the back and lateral faces of the neck, in the armpits, and groin. There were clinical data of hyperandrogenism (acne, hirsutism, and male-pattern hair loss). Laboratory tests reported hemoglobin 11.7 g/dL, white blood cells 8.4 CC3, serum glucose 203 mg/dL, creatinine 0.4 mg/dL, albumin 2.2 g/dL with no alteration in liver transaminases and serum electrolytes. Urinalysis was remarkable for proteinuria 30 mg/dL, glucosuria 500 mg/dL with no erythrocytes and leucocytes. The patient was tested for COVID-19 due to her respiratory symptoms. A SARS-CoV-2 PCR test was positive.
      Fasting and a basal plus scheme with a dose of 20 IU of NPH insulin and betamethasone for fetal lung-maturation (12 mg intramuscularly) were started. The fetus was monitored with cardiotocography (CTG). After 10 h, the fetus showed signs of fetal distress on the CTG, and a C-section was performed. A male newborn was delivered. He weighed 2630 g (P > 97%) with an Apgar of 1/3. CPR was given with the return of spontaneous circulation after three cycles. The newborn was then transferred to the neonatal intensive care unit, where he was tested for SARS-CoV2 with a negative result. He persisted with cardiogenic shock secondary to a double outlet right ventricle. The newborn persisted hypotensive and acidotic and passed away three days after delivery.
      Our patient remained under surveillance after delivery. We changed the insulin scheme to NPH 10 IU BID, but two days after delivery, she had two asymptomatic hypoglycemia episodes (65 mg/dl and 62 mg/dl). We decided to suspend the basal insulin scheme and continue glucose monitoring without additional insulin therapy. The patient was isolated for five days in our hospital without supplemental oxygen and no sign of respiratory distress. She was discharged with the indication of continuing home isolation and was scheduled for an oral glucose tolerance test and follow-up in 8 weeks.

      2. Discussion

      Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycemia detected for the first time during pregnancy. Hyperglycemia during pregnancy is associated with a higher risk of negative maternal and newborn outcomes [
      • Dirar A.M.
      • Doupis J.
      Gestational diabetes from A to Z.
      ]. The most frequent maternal negative outcomes are preeclampsia and cesarean delivery, and the newborn’s reported outcomes are preterm delivery, neonatal hypoglycemia, neonatal intensive unit care, and macrosomia [
      • Group H.S.C.R.
      • et al.
      Hyperglycemia and adverse pregnancy outcomes.
      ].
      As the global pandemic continues with an exponential increase in COVID-19 cases (caused by the SARS-CoV-2 virus), these cases may be associated with negative outcomes in certain high-risk groups, such as patients with chronic-degenerative diseases, oncological diseases, and pregnant women [
      • Qiancheng X.
      • Jian S.
      • Lingling P.
      • et al.
      International Journal of Infectious Diseases Coronavirus disease 2019 in pregnancy.
      ]. At the start of 2020, new evidence in the form of case series became available online. Later large observational studies described the clinical characteristics and outcomes of pregnant women with COVID-19 [
      • Ellington S.
      • Strid P.
      • Tong V.
      • et al.
      Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status — United States, January 22-June 7, 2020.
      ,
      • Yan J.
      • Guo J.
      • Fan
      • et al.
      Coronavirus disease 2019 (COVID-19) in pregnant women: a report based on 116 cases.
      ]. The prevalence of COVID-19 in pregnant women varies with the series, with an overall rate of 10% (7–14%) [
      • Allotey J.
      • Stallings E.
      • Bonet M.
      • et al.
      Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.
      ]. The prevalence of GDM varies between 7.5 and 11.6% in the most extensive series [
      • Yan J.
      • Guo J.
      • Fan
      • et al.
      Coronavirus disease 2019 (COVID-19) in pregnant women: a report based on 116 cases.
      ,
      • Kayem G.
      • Lecarpentier E.
      • Deruelle P.
      • et al.
      A snapshot of the Covid-19 pandemic among pregnant women in France.
      ]; however, an analysis of clinical characteristics and prognosis in this subgroup is not available within most extensive series. They are only available in case reports or small case series.
      Pregnant women with confirmed COVID-19 have more complications than non-pregnant women of the same age and disease [
      • Collin J.
      • Byström E.
      • Carnahan A.
      • et al.
      Public Health Agency of Sweden’s Brief Report: pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in intensive care in Sweden.
      ]. There is an increased risk of hospitalization (5.4 times), mechanical ventilation (1.7 times), and ICU admission (1.5 times), but there was no difference regarding mortality [
      • Ellington S.
      • Strid P.
      • Tong V.
      • et al.
      Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status — United States, January 22-June 7, 2020.
      ]. The presence of older age (>35 years) and comorbidities (obesity, chronic hypertension, and preeclampsia) are risks factors associated with a more severe clinical presentation of COVID-19 in pregnancy [
      • Guan W.
      • Liang W.
      • Zhao Y.
      • et al.
      Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.
      ] and with a worse maternal-fetal prognosis, such as preterm birth (before week 37th), fetal distress, and cesarean delivery [
      • Yan J.
      • Guo J.
      • Fan
      • et al.
      Coronavirus disease 2019 (COVID-19) in pregnant women: a report based on 116 cases.
      ,
      • Kayem G.
      • Lecarpentier E.
      • Deruelle P.
      • et al.
      A snapshot of the Covid-19 pandemic among pregnant women in France.
      ,
      • Knight M.
      • Bunch K.
      • Vousden N.
      • et al.
      Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population-based cohort study.
      ]. The most frequent symptoms in pregnancy depend on the screening criteria. When symptomatic pregnant women were screened, the symptoms were cough (71.4%), fever (63.4%), shortness of breath (34.4%), and loss of taste or smell (22.9%) [
      • Khalil A.
      • Kalafat E.
      • Benlioglu C.
      • et al.
      SARS-CoV-2 infection in pregnancy: a systematic review and meta- analysis of clinical features and pregnancy outcomes.
      ]; however, when universal screening was applied, the number of symptoms was lower with cough and fever still being the most frequent (39–40%). This finding may be explained by more asymptomatic presentations or a lower rate of symptomatic presentations in pregnant women compared to non-pregnant women [
      • Allotey J.
      • Stallings E.
      • Bonet M.
      • et al.
      Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.
      ].
      We describe the clinical characteristics of women with GDM and laboratory-confirmed COVID-19 in Table 1 [
      • Liu W.
      • Wang Q.
      • Zhang Q.
      • et al.
      Coronavirus disease 2019 (COVID-19) during pregnancy: a case series.
      ,
      • Gidlöf S.
      • Savchenko J.
      • Brune T.
      • et al.
      COVID-19 in pregnancy with comorbidities: more liberal testing strategy is needed.
      ,
      • Kleinwechter H.
      • Laubner K.
      Coronaviruserkrankung 2019 (COVID-19) und Schwangerschaft.
      ]. The mean age was 28 years, mean gestational age was 32.2 weeks, cough was the most prevalent initial symptom, the majority were preterm cesarean deliveries, all patients made a complete recovery. There was no vertical transmission, and one newborn died secondary to a cardiac anomaly.
      Table 1Clinical characteristics of patients with GDM and laboratory confirmed COVID-19.
      CaseReferenceCountryAgeClinical presentation/ chest X-rayGestational week/deliveryPregnancy complicationsTreatmentMaternal outcomeNewborn transmission/outcome
      1Liu W at al. (2020) [
      • Liu W.
      • Wang Q.
      • Zhang Q.
      • et al.
      Coronavirus disease 2019 (COVID-19) during pregnancy: a case series.
      ]
      China30Cough/Subsolid patchy and linear fibrosis in the left lung37/VaginalNoneOxygen via nasal cannula and arbidol hydrochloride 3 g, QIDRecoveredNegative/recovered
      2Gidlöf S et al. (2020) [
      • Gidlöf S.
      • Savchenko J.
      • Brune T.
      • et al.
      COVID-19 in pregnancy with comorbidities: more liberal testing strategy is needed.
      ]
      Sweden34Mild headache, hoarseness and malaise/ not reported36 (twin pregnancy)/CesareanPreeclampsiaOxygen via nasal cannulaRecoveredNegative/recovered
      3Kleinwechter H et al. (2020) [
      • Kleinwechter H.
      • Laubner K.
      Coronaviruserkrankung 2019 (COVID-19) und Schwangerschaft.
      ]
      Germany28Fever and cough/not reported25.6/not deliveredVaginal bleedingOxygen via nasal cannula/TocolyticsRecoveredNegative/recovered
      4Actual CaseMexico20Cough/ normal30/CesareanFetal distressNo supplemental Oxygen neededRecoveredNegative/death
      GDM: gestational diabetes mellitus.
      Negative newborn outcomes defined as preterm delivery, hypoglycemia, macrosomia, and the need for NICU management is higher than with non-COVID-19 pregnant women; however, there is not enough information to make a statement regarding women with GDM and COVID-19. Last, mortality is usually low according to the literature (0.5%–1%); however, it depends mostly on the severity of the maternal complications [
      • Kayem G.
      • Lecarpentier E.
      • Deruelle P.
      • et al.
      A snapshot of the Covid-19 pandemic among pregnant women in France.
      ,
      • Knight M.
      • Bunch K.
      • Vousden N.
      • et al.
      Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population-based cohort study.
      ,
      • Zhang L.
      • Jiang Y.
      • Wei M.
      • et al.
      ].
      We described the clinical characteristics and the maternal-fetal prognosis of women with GDM and COVID-19; even though there were only 4 cases, they had a similar clinical evolution, and all four recovered from COVID-19. We suspect that the unfortunate outcome of the newborn in our case was associated more to the maternal comorbidities (GDM and obesity) than to COVID-19; however, there is still a lack of information regarding this subgroup of patients; thus, we hope this case and the evidence described above can be of assistance for our colleagues.

      Author contribution

      All authors had full access to data and a roll in the preparation of this manuscript.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Ethical consent

      Ethical consent was complied. We received verbal consent from the patient to give details about the case.

      Conflict of interest

      None.

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