COVID-19 vaccine and non-syndromic orofacial clefts in five arab countries. A case-control study.

OBJECTIVES: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries. MATERIALS AND METHODS: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting. RESULTS: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006). CONCLUSION: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly. CLINICAL RELEVANCE: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants.

COVID-19 related risk factors and their association with non-syndromic orofacial clefts in five Arab countries: a case-control study.

BACKGROUND: The environmental etiology of non-syndromic orofacial clefts (NSOFCs) is still under research. The aim of this case-control study is to assess COVID-19 associated factors that may be related to the risk of NSOFC in five Arab countries. These factors include COVID-19 infection, COVID-19 symptoms, family member or friends infected with COVID-19, stress, smoking, socioeconomic status and fear of COVID-19. METHODS: The study took place in governmental hospitals in five Arab countries from November 2020 to November 2021. Controls are matched in the month of delivery and site of recruitment. A clinical examination was carried out using LASHAL classification. Maternal exposure to medication, illnesses, supplementation, COVID-19 infection during their pregestation and 1st trimester periods were evaluated using a validated questionnaire. Maternal exposure to stress was assessed using the Life Events scale, fear of covid-19 scale, family member or friend affected with covid-19 infection, pregnancy planning and threatened abortion. RESULTS: The study recruited 1135 infants (386 NSOFC and 749 controls). Living in urban areas, maternal exposure to medications 3-months pregestation, maternal exposure to any of the prenatal life events and maternal fear of COVID-19 significantly increased the risk of having a child with NSOFC. On the other hand, mothers exposed to supplementation 3-months pregestation, mothers suspected of having COVID-19 infection, family members or friends testing positive with COVID-19 significantly decreased the risk of having a child with NSOFC. CONCLUSIONS: This study suggests that NSOFC may be associated with maternal exposure to lifetime stress and COVID-19 fear in particular, with no direct effect of the COVID-19 infection itself. This highlights the importance of providing psychological support for expecting mothers during stressful events that affect populations such as the COVID-19 pandemic, in addition to the usual antenatal care.

Coronavirus Infection in Neonates: Neurodevelopmental Outcomes at 18 Months of Age.

Background: Although most neonates with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection experience only mild disease, its impact on neurodevelopmental outcomes is unknown. This study aimed to assess the 18-month neurodevelopmental outcomes of infants who had SARS-CoV-2 infection as neonates. Methods: The authors conducted a prospective cohort study of neonates diagnosed with SARS-CoV-2 infection from June 2020 to December 2020 through nasopharyngeal coronavirus disease 2019 (COVID-19). A total of 58 neonates were identified from the Kuwait National COVID-19 Registry and enrolled. Historical controls were selected from the neonatal follow-up registry and matched in a 2 : 1 ratio based on sex and gestational age. When the subjects were 18 months of age, their neurodevelopmental outcomes were assessed by two trained assessors using the Bayley Scales of Infant and Toddler Development-3rd Edition (BSID-III). Results: Forty children diagnosed with SARS-CoV-2 infection were included in the final analysis. The median age at infection was 18 days (range: 10-26 days). Eighteen (45%) patients were asymptomatic, 15 (37.5%) had a sepsis-like presentation, 5 (12.5%) exhibited respiratory distress, and 2 (5%) had a multisystem inflammatory syndrome in children (MIS-C)-like presentation. At the 18 months follow-up, only one child showed a severe developmental delay and one child had a language delay. BSID-III outcomes did not differ significantly between the SARS-CoV-2-infected and control groups. Conclusions: There was no difference in neurodevelopmental outcomes at 18 months in children infected with SARS-CoV-2 compared with controls, although longer neurodevelopmental follow-up studies are required.

Neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections during pregnancy: a national prospective study in Kuwait.

BACKGROUND: An increasing proportion of women are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study was to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy. METHODS: In this prospective cohort study, the neurodevelopmental status of infants (N = 298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff scores ≤ 2 standard deviations (SDs) below the population mean) and no delays (scores > 2 SDs above the population mean). RESULTS: The majority (90%) of the infants born to mothers with SARS-CoV-2 infections during pregnancy had favorable outcomes and only 10% showed developmental delays. Two of the 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infections during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P = 0.039) and second trimesters (P = 0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. CONCLUSION: The neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections seem favorable. However, more studies with larger sample sizes and longer follow-up periods are required.

Late-onset Sepsis in Preterm Neonates is Associated with Higher Risks of Cerebellar Hemorrhage and Lower Motor Scores at Three Years of Age.

Objectives: To evaluate the impact of late-onset sepsis (LOS) in preterm infants on brain injury and neurodevelopmental outcomes at 36 months corrected age (CA). Methods: We retrospectively analyzed the medical records of 203 preterm neonates of 24-32 weeks gestational age who were admitted between January and December 2017 at the neonatal intensive care unit (NICU) of a maternity hospital in Kuwait. The cases were stratified into no sepsis, early-onset sepsis (first onset of sepsis ≤ 72 hours postnatally), and LOS (> 72 hours postnatally). Brain injury was assessed from MRI records. Neurodevelopmental outcomes were evaluated at 36 months CA using Bayley-III scales of infant development. Results: Out of 203 neonates, 16 had early-onset sepsis with Klebsiella pneumonia and group B streptococcus, and 93 developed LOS with K. pneumonia and gram-positive cocci in clusters. There were no group-wise differences in the prevalence of intraventricular hemorrhage (n = 68) or white matter injury (n = 42). However, higher cerebellar hemorrhage risk (adjusted odds ratio = 4.6 (1.3-18.6; p = 0.030) was observed in LOS group. At 36 months CA, infants in the LOS group were more likely to have lower motor, cognitive, and language composite scores. After adjusting for gestational age, birth weight, cerebellar hemorrhage, and white matter injury, the relationship between LOS and lower motor scores remained significant (adjusted ß = -9.5, 95% CI: -16.4 to -2.7; p = 0.007), whereas the association with cognitive and language scores were no longer significant. Conclusions: LOS in preterm neonates significantly raises the risk of cerebellar hemorrhage and lower motor scores by three years of age.

COVID-19 convalescent plasma treatment of moderate and severe cases of SARS-CoV-2 infection: A multicenter interventional study.

OBJECTIVE: To study the effectiveness of COVID-19 convalescent plasma (CCP) therapy for patients with moderate and severe COVID-19 disease. METHODS: This non-randomized prospective cohort study was conducted from May 21 to June 30, 2020, at four major tertiary hospitals in Kuwait. CCP was administered to 135 patients. The control group comprised 233 patients who received standard treatment. All patients (N = 368, median age 54 [range 15-82]) had laboratory-confirmed SARS-CoV-2 infection and either moderate or severe COVID-19 disease. RESULTS: CCP treatment was associated with a higher rate of clinical improvement in patients with moderate or severe disease. Among those with moderate COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 8 days in the control group (p = 0·006). For severe COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 15.5 days in the control group (p = 0·003). In the adjusted analysis, patients with moderate disease treated with CCP had a significantly lower 30-day mortality rate. Compared to the control group, oxygen saturation improved within 3 days of CCP transfusion, and lymphocyte counts improved from day 7 in patients with moderate COVID-19 disease and day 11 in patients with severe disease. C-reactive protein levels declined throughout the first 14 days after CCP transfusion. None of the CCP patients developed a serious transfusion reaction. CONCLUSIONS: The data show that administration of CCP is a safe treatment option for patients with COVID-19 disease with a favorable outcome in the rate of, and time to, clinical improvement.

Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait.

BACKGROUND: The effect of SARS-CoV-2 infection in pregnant women and newborns is incompletely understood. Preliminary data shows a rather fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. However, it is not clear whether the disease increases the risk of pregnancy-related complications. The aim of the study is to describe the maternal and neonatal clinical characteristics and outcome of pregnancies with SARS-CoV-2 infection. METHODS: In this retrospective national-based study, we analyzed the medical records of all pregnant women infected with SARS-CoV-2 and their neonates who were admitted to New-Jahra Hospital (NJH), Kuwait, between March 15th 2020 and May 31st 2020. During the study period and as part of the public health measures, a total of 185 pregnant women infected with SARS-CoV-2, regardless of symptoms, were hospitalized at NJH, and were included. Maternal and neonatal clinical manifestations, laboratory tests and treatments were collected. The outcomes of pregnancies included miscarriage, intrauterine fetal death (IUFD), preterm birth and live birth were assessed until the end date of the outcomes follow-up (November 10th 2020). RESULTS: A total of 185 pregnant women infected with SARS-CoV-2 were enrolled with a median age of 31 years (interquartile range, IQR: 27.5-34), and median gestational age at diagnosis of SARS-CoV2 infection was 29 weeks (IQR: 18-34). The majority (88%) of these women had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). At the time of the analysis, out of the 185, 3 (1.6%) of the pregnant women had a miscarriage, 1 (0.54%) had IUFD which was not related to COVID-19, 16 (8.6%) had ongoing pregnancies and 165 (89%) had a live birth. Only 2 (1.1%) of these women developed severe pneumonia and required intensive care. A total of 167 neonates with two sets of twins were born with median gestational age at birth was 38 (IQR: 36-39) weeks. Most of the neonates were asymptomatic, and only 2 of them tested positive on day 5 by nasopharyngeal swab testing. CONCLUSIONS: In this national-based study, most of the pregnant women infected with SARS-CoV-2 showed mild symptoms. Although mother-to-child vertical transmission of SARS-CoV-2 is possible, COVID-19 infection during pregnancy may not lead to unfavorable maternal and neonatal outcomes.