Effects of COVID-19 Infection on the Fetus

ABSTRACT

Objective: To find out the antimicrobial resistance pattern in A. baumannii isolates from sputum samples of hospitalized patients in ICUs and determine the incidence rates of most common OXA-type carbapenemases, NDM-1, KPC and Class1 integrons among A. baumannii isolates. 

 Methods: This retrospective study included a total of 50 A. baumannii isolates recovered from sputum specimens, obtained from adult ICU patients at King Hussein Medical Center (KHMC, Amman, Jordan) over a period of 18-months from February 2017 to August 2018. All isolates were identified and tested for susceptibility against 13 antibiotics by VITEK 2 Automated Microbiology System using gram negative ID card and “VITEK 2 AST–N233 and AST-XNO5 susceptibility cards according to CLSI guidelines (2018). Genomic and plasmid DNA were extracted. PCR tests were used to determine the presence of six types of class D oxacillinases, one type of class A carbapenemases, one type of class B metallo β lactamases, and Class 1 Integron among MDR isolates.

Results: All 50 isolates were MDR, including 100% resistance to cephalosporins, ciprofloxacin, aztreonem, piperacillin/tazobactum, 94%-98% to carbapenemes and 2% to colistin. All isolates carried blaOXA-51 and 94% were positive for blaOXA-23, while blaOXA-24, blaOXA-58, blaOXA-143 and blaOXA-235 were positive in smaller percentages (4%-12%). The isolates also were positive for NDM-1, KPC and Class 1 Integron at rates of 26%, 22% and 86%, respectively.

Conclusions: This study concludes that respiratory tract colonization must be taken seriously as a source of bacteraemia with aggressive MDR A. baumannii. In addition, A. baumannii are able to acquire a lot of genetic resistance factors which will cause difficulties in treatment and rapid transmission in hospitals, Therefore, healthcare facilities should follow infection control measures

to control and stop the transmission of MDR organisms.

Keywords: Acinetobacter baumannii, MDR, PCR, bla OXA, Class1 Integron.

RMS April 2023; 30 (1): 10.12816/0061488

Methods

This was a retrospective case-control study conducted in the obstetrics and gynecology department of Queen Alia Hospital, Amman, Jordan, between January 1 and March 31, 2022. The positive cases included in this study (80 women) were either patients who were admitted for delivery and tested positive for COVID-19 or who were admitted due to symptomatic infection.47 patients (59%) were asymptomatic or 33 patients (41%) were symptomatic. All patients were diagnosed by polymerase chain reaction using nasopharyngeal swabs. The control group patients (80 women) were recruited from the antenatal care clinic at Queen Alia Hospital, where a rapid antigen test was performed on all patients prior to ultrasound examination. Inclusion criteria: maternal age 18–44 years, gestational age 24–40 weeks, and singleton pregnancy. Exclusion criteria: severe cases of COVID-19 infection that required intensive care unit (ICU) admission, multiple gestations, patients known to have fetal anomalies prior to the study, and patients receiving medications that may affect the fetus, such as anti-epileptics.

Fetal biometry, amniotic fluid index (AFI), and Doppler studies were performed on all patients by a fetal medicine specialist following the guidelines of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) ⁽⁵⁾. An ultrasound examination was done as soon as the infection was confirmed. Sonographic parameters: Biparietal diameter (BPD), head circumference (HC), femur length (FL), and abdominal circumference (AC) were used to estimate the fetal weight. An estimated fetal weight (EFWT) < 10th percentile for gestational age was considered as small for gestational age (SGA). An AFI < 5 or > 25 was considered abnormal.

Doppler velocimetry included umbilical artery Doppler (UAD), middle cerebral artery Doppler (MAD), and cerebroplacental ratio (CPR). The umbilical artery pulsatility index (UA-PI) > 95th percentile for gestational age was considered abnormal. The middle cerebral artery pulsatility index (MCA-PI) and CPR < 5^th percentile for gestational age were considered abnormal ⁽⁶⁾. 

  Co-morbidities (DM, HTN, hypothyroidism, anemia, and asthma) were reported and compared between both groups.

Data were analyzed statistically using SPSS software. Measured variables were expressed as mean +- standard deviation or as a percentage. The statistical significance of the variables was tested using the P-value. P-values were considered significant only if they were less than 0.05.

Ethical approval was obtained from the ethical committee of Royal Medical Services before starting the study.

Results 

 Data collected from 80 positive cases and 80 negative controls were analyzed and compared.

The clinical characteristics of the patients are shown in Table I.

Table I: Clinical characteristics of the patients

According to the independent sample T-test

The mean age in the positive group was 29.55 years compared to 30.46 years in the negative group (P=0.302). The mean parity in the positive group was 2.99 compared to 2.65 in the negative group (P=0.178). Gestational age at ultrasound examination was higher in the positive group (32.75 weeks compared to 29.79 weeks in the negative group), P=0.000.

The associated co-morbidities are shown in Table II.

Table II: Associated Morbidities

According to the Chi-squared test

The prevalence of DM was higher in the positive group (16.3%) compared to (13.8%) in the negative group but not significant, P= 0.825. Prevalence of HTN wasn’t significantly different between positive patients (12.5%) and controls (11.3%), P= 0.999. 3.8% of positive patients had Hypothyroidism compared to 2.5% in the negative group, P = 0.999. Anemia was comparable between positive and negative groups (15%, 13.8%) respectively, P = 0.999. Respiratory diseases were more prevalent in the positive group (3.8%) compared to (1.3%) in the negative group, P = 0.62 but not statistically significant

.

Doppler indices are shown in Table III.

Table III:  Doppler indices.

 UA-PI: uterine artery pulsatility index

MCA -PI: pulsatility index

CPR: Cerebroplacental ratio

AFI: Amniotic fluid index

According to the independent sample T-test

The mean UA-PI was 1.06 in the positive group compared to 1.05 in the controls, P = 0.628. And the mean MCA-PI was 1.5 in the positive group and 1.48 in the negative group, P = 0.654. No difference in CPR between both groups (1.45, 1.45) respectively, P = 0.900.

Ultrasound Findings are shown in Table IV.

Table IV:  Ultrasound findings 

According to the Chi-squared test

Three cases of SGA were encountered in the positive group (3.8%); two of them were associated with pre-eclampsia toxemia and were managed according to obstetric protocols. The third case was an isolated SGA with normal AFI and Doppler studies. Two cases of SGA were encountered in the negative group (2.5%), P = 0.999.

Three cases of oligohydramnios were encountered in the positive group (3.8%); one for a case of preterm premature rupture of membrane (PPROM) and two cases were associated with hypertensive disorders of pregnancy. Two cases of oligohydramnios were encountered in the negative group (2.5%), P = 0.999.

One case of polyhydramnios in the positive group (1.3%) was associated with uncontrolled DM. Two cases of polyhydramnios in the negative group (2.5%), P = 0.999.

   No cases of IUFD were found in both groups.

Discussion

This study was conducted to address the possible consequences of COVID-19 infection on fetal well-being. After analyzing our data, we found that both positive and negative groups were comparable in all parameters with no significant differences except in the gestational age which is considered a limitation of this study.

E. Soto-Torres et al in a retrospective case-control study released in Jul 2021 showed that no significant differences in fetal ultrasound and Doppler findings between pregnant women who were positive for Covid-19 and the controls ⁽⁷⁾.

Another study that was published in the International Journal of Medical Sciences in Jan 2021 by Chiu-Lin Wang et alconcluded that Covid-19 infection in pregnant women doesn’t increase the risk of intrauterine deaths or IUGR ⁽⁸⁾.

However, Shu Qin Wei et al in a systematic review published in Canadian Medical Association Journal in April 2021 showed that Covid-19 infection in pregnancy was associated with low birth weight and increased risk of preeclampsia and other adverse pregnancy outcomes ⁽⁹⁾.

Another study by Vincenzo Berghella published in the American Journal of Obstetrics and Gynecology in Nov 2020showed that in-utero transmission is rare and rates of miscarriages and congenital anomalies are not increased in pregnancies affected by Covid-19, and the neonatal outcome is generally good ^(10).

Mehreen et al in a systematic review published in April 2020 found that one of 75 newborns tested was positive for Covid-19but this baby did well clinically ^(11).

Currently, there is not enough evidence of vertical transmission of the COVID-19 virus during pregnancy ⁽¹²⁾. Apart from thevertical transmission of the disease, excessive inflammation, vascular injury, and impaired perfusion may affect the fetomaternal circulation in the absence of direct fetal infection. Histopathological examination of the placentae obtained from COVID-19-positive women showed an increased prevalence of microcalcification and fibrin thrombi, which may reflect an underlying hypercoagulable state induced by the infection ⁽¹³⁾. Pathological processes that interact with the vascular structure of the placenta and maternal hypoxia have been reported to cause impaired Doppler findings. Placental endothelial injury and hypoxemia cause high resistance in fetal circulation, which can be measured non-invasively by Doppler indices ^{(14, 15)}Despite our initial assumption, we didn’t find significant differences in UA-PI, MCA-PI, and CPR between both groups. COVID-19 infection may affect the microscopic structures of the placenta without clinical significance. However, more studies are needed to confirm these findings

Conclusion

According to our results, there were no significant differences in fetal ultrasound findings and fetal Doppler indices between positive and negative pregnant women. COVID-19 infection seems to have no adverse effects on fetal well-being. However, the full impact of infection on pregnancy remains to be determined by further studies.

Limitations of this study are the small number of cases and the difference in the gestational age between both groups. Also, the ultrasound examination was done soon after the infection so the study evaluates only the immediate changes of Covid-19 on the amniotic fluid and fetal Doppler’s.

References

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6. Sule Goncu Ayhan et al. Assessment of fetal doppler parameters in pregnant women with Covid 19 infection, a prospective case control study, 2021

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14. Allotey J et al. Clinical manifestations, risk factors and perinatal outcomes of corona virus disease in pregnancy 

15. Karimi-Zarci M et al. Vertical transmission of Coronavirus 19 disease from infected mothers to neonates

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