The Effects and Outcomes of the COVID-19 Pandemic on Pregnant Women in Kuwait.

OBJECTIVES: This retrospective study reports the effects of COVID-19 among hospitalized pregnant women infected with COVID-19 and compares them to a control group. METHODS: A multi-center retrospective cohort study, in which data of pregnant women with COVID-19, admitted to five different hospitals in Kuwait, were collected. Two groups were included, the first group were women with COVID-19 who were admitted between March 22, 2020 until December 31, December 2020. The second (control) group included pregnant women without COVID-19, who were admitted between March 1, 2019 and March 21, 2020. Data were collected using a standardized data collection survey, entered using Excel Software and analyzed using Analysis of Variance (ANOVA). RESULTS: We compared 764 patients, with confirmed COVID-19 with 765 uninfected control subjects. The majority of pregnant women were diagnosed with COVID-19 infection during the third trimester. Tachycardia was the most frequent sign at admission and dry cough and fever were the most common presenting symptoms. ICU admission and respiratory failure were significantly higher in the COVID-19 group. Cesarean section (CS) rate was higher in the COVID-19 group, with obstetric and maternal complications being the most common indications in comparison to fetal indications in the control group. CONCLUSIONS: This study was conducted to identify the effects of COVID-19 in pregnancy. Most patients were asymptomatic. The rate of normal vaginal delivery was higher in the control group. The main indications for Cesarean section in the COVID-19 group were obstetrical and maternal complications compared to fetal complications in the control group. .

The effect of COVID-19 lockdown on admission rates in Maternity Hospital.

Objectives: The COVID-19 pandemic had adverse health outcomes on individuals and communities. In this cross-sectional study we evaluated the admission rates in a tertiary-level hospital during the first wave of the pandemic (March 22, 2020 to August 31, 2020). Methods: We compared the indications for admission during the first wave of the pandemic to a control period prior to the lockdown (November 9, 2019 to March 22, 2020). Results: Most hospital admissions during the curfew period were obstetric emergencies (46.88%), which were significantly higher than the control group (38.19%) p ≤ 0.0001. Among the obstetric emergencies, cases in active labor (65.63%) were dominant. Significant rises in car deliveries (2.46%, p ≤ 0.0001) and admissions during the second stage of labor (6.43%, p ≤ 0.001) were noted. There was also an increased rate of admissions for early pregnancy complications, induction of labor, elective obstetric cases, and medical obstetric cases. Conclusions: This study demonstrates that lockdown precautions implemented had a significant impact on the rate of admissions to Maternity Hospital. The data obtained may be a used to aid in designing robust policies for future pandemics to avoid adverse health outcomes.

Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait.

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.

Prevalence of cytomegalovirus DNA in cord blood and voided urine obtained from pregnant women at the end of pregnancy.

OBJECTIVE: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. SUBJECTS AND METHODS: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤10(3) copies/µl, intermediate when the viral load = 10(3)-10(4) copies/µl, and high when the viral load >10(4) copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. RESULTS: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. CONCLUSION: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.

The scope of pediatric and adolescent gynecological problems in Kuwait.

OBJECTIVE: To establish an insight into pediatric and adolescent gynecological disorders encountered in a tertiary care center in Kuwait. SUBJECTS AND METHODS: A retrospective case cohort review of 89 case records of patients under the age of 19 years who were admitted to the Maternity Hospital, Kuwait, from October 2002 through September 2003 was undertaken. For a variety of reasons, 35 patients were excluded and the remaining 54 patients constituted the study population. The patients were divided into 5 groups (A-E): group A = ovarian cysts, group B = disorders of pregnancy, group C = menstrual disorders, group D = gynecological infections and group E = miscellaneous. The clinical presentation and management of patients were analyzed. RESULTS: The following spectrum of gynecological disorders was obtained: 13 ovarian cysts (24.1%), 28 disorders of pregnancy (51.8%), 4 menstrual disorders (7.4%), 2 infections (3.7%) and 7 miscellaneous cases (13.9%). Of the 54 patients, 36 (66.7%) were Kuwaitis and the remaining 18 (33.3%) were non-Kuwaitis. The mean age of the study population was 15.16 years, the median was 15.5 years, and the range was 8-19 years. The mean age of the patients with disorders of pregnancy was 17.52 +/- 1.16 years, which is significantly higher than that of groups A, C and E (p = 0.007, 0.0001 and 0.05). The main presenting symptoms at admission were vaginal bleeding: 31 (57.4%), abdominal pain: 17 (31.5%), abdominal mass: 10 (18.5%), and vomiting: 10 (18.5%). Ultrasonography revealed that dermoid cysts were the most frequently encountered ovarian cysts. Patients were hospitalized for 1-7 days. CONCLUSION: Disorders of pregnancy and ovarian cysts were the most frequently encountered pediatric/adolescent gynecological disorders. It is recommended that there should be a dedicated specialized clinic to guarantee privacy and centralized discreet care for these patients.

Maternal-fetal transport kinetics of methotrexate in perfused human placenta: in vitro study.

OBJECTIVE: Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro. METHODS: Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters. RESULTS: Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Student's t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Student's t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.

Maternal-fetal transport kinetics of carboplatin in the perfused human placental lobule: in vitro study.

OBJECTIVE: Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal-fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro. METHODS: Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 +/- 0.10, 1.06 +/- 0.06, 1.00 +/- 0.02, 0.98 +/- 0.01, and 0.99 +/- 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.60 +/- 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.

Increasing severity of haematuria with successive pregnancies in a woman with renal angiomyolipoma.

OBJECTIVE: To report a case of a 31-year-old woman with renal angiomyolipoma (RAML) who presented with progressive massive haematuria with successive pregnancies. CLINICAL PRESENTATION: A 28-year-old woman presented with mild haematuria in the third trimester of her second pregnancy. This was due to bleeding from a left RAML. Patient became pregnant for a third time. The RAML increased in size and patient bled more during the third trimester. After delivery she refused partial nephrectomy or renal embolisation. In the third trimester of the fourth pregnancy, she presented with massive haematuria, shock, severe anaemia (haemoglobin of 6gm/l) and required a total of 26 units of blood transfusion during a 4-week period. She required emergency Caesarian section at 36 weeks and simple nephrectomy 3 months postpartum. CONCLUSION: The risk of profuse haemorrhage from RAML may increase with successive pregnancies in women with RAML. This anomaly should be treated in between pregnancies by either angioembolisation or resectional surgery.

Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation.

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the maternal vein of the obese group (3.60 +/- 0.20) was significantly lower (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however, Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.

Motor-vehicle injury in pregnancy and subsequent feto-maternal outcomes: of grave concern.

OBJECTIVES: (1) To evaluate maternal and fetal outcome after motor-vehicle injury during pregnancy. (2) To determine if there was prenatal care provider counseling for seat belt use. METHODS: Retrospective chart analysis of materno-fetal outcome following motor vehicle injury in 728 pregnant women between 2009 and 2012. Women attending antenatal clinics over these years were asked if they were counseled regarding correct seat belt use by prenatal health care providers during their antenatal visits. RESULTS: In these pregnant women, 80 (11%) sustained minor injuries/sprains. 648 women (89%) had severe adverse materno-fetal pregnancy outcomes. Important causes being: (1) placental abruption 58.8%; (2) preterm labor (40%); and (3) uterine rupture (1.6%). There were 100 (13.7%) maternal and 78 (10.7%) fetal deaths. 91 (12.5%) perimortem cesarean deliveries were performed and 74 (81%) fetus survived, as did 31 women. Prenatal care provider counseling for seat belt use occurred in 44.8% of prenatal visit. Only 125 (21%) were using seat belt during the accident. CONCLUSION: Important causes of adverse pregnancy outcome were: abruptio placenta, preterm labor and uterine rupture. There were 100 maternal and 78 fetal deaths with 97 preterm births. Counseling occurred in 44.8% of women. Those using seat belts during the accidents sustained minor injuries.

Induction of labor in grand multiparous women with previous cesarean delivery: how safe is this?

OBJECTIVE: To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed. METHODS: In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS. RESULTS: There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%). CONCLUSION: In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.

Is membrane sweeping beneficial at the initiation of labor induction?

OBJECTIVE: To determine whether cervical membrane sweeping during labor induction is beneficial. METHODS: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes "swept" or "not swept" at the initiation of labor induction. RESULTS: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 "swept", 202 "not swept"] and 400 multiparas (Group B) (201 "swept" and 199 "not swept"]. Among group A who received intravaginal prostaglandin (PG) E2, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9 ± 1.3 versus 16.2 ± 1.1 hours, p = 0.046), lower mean dose of oxytocin (6.6 ± 0.6 versus 10.11 ± 1.4 mU/minute, p = 0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p = 0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9 ± 2.9 versus 10.9 ± 2.6 hours p = 0.04, mean maximum dose of oxytocin 9.8 ± 1.1 versus 15.2 ± 1.1 mU/min, p = 0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping. CONCLUSION: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE2 or Oxytocin alone.

Viral load of human papillomavirus in women with normal and abnormal cervical cytology in Kuwait.

INTRODUCTION: Human papillomaviruses (HPV) are the most commonly known sexually transmitted agents. Almost all cases of cervical cancer are caused by persistent infection. This study was conducted to ascertain whether there is a difference in HPV load in cervical samples with normal and abnormal cervical cytology reports in Kuwait. METHODOLOGY: HPV-positive abnormal ThinPrep samples (n = 206) and normal ThinPrep samples (n = 120) were taken from women attending gynecology clinics. Real-time PCR was used to measure the viral load for all HPV genotypes. RESULTS: The median normalized viral load in samples with normal and abnormal cytology reports was 0.86 × 10-7 and 4.66 × 10-7, respectively (p = 0.001). Median normalized viral load of high-risk (HR), intermediate-risk (IR) and low-risk (LR) HPV was 4.04 × 10-7, 0.71 × 10-7 and 2.38 × 10-7, respectively, (p = 0.002). CONCLUSIONS: The findings suggest that, in the absence of a proper screening programme in Kuwait, quantification of HPV viral load could be considered as a surrogate virology test to identify women with abnormal cytology. Further population-based prospective studies are needed to include more women with high-grade and invasive carcinoma reports.

Uterine rupture and subsequent pregnancy outcome--how safe is it? A 25-year study.

OBJECTIVES: (a) To review the cases of ruptured uterus over the last 25 years and analyze the causative factors with a view to its prevention (b) To analyze subsequent pregnancy outcome with a view to its safety. METHOD: The case notes were reviewed for all patients with ruptured uterus over a period of 25 years from January 1982 to January 2007. Relevant dates relating to the characteristics of labor, delivery, maternal, perinatal, and subsequent pregnancy outcomes were assessed. RESULTS: The incidence of ruptured uteri was calculated to be 0.03%. Total deliveries included in the study were 152,426. There were 46 cases of ruptured uteri and 44 were available for study. Twenty-two (52%) ruptured uteri occurred in patients with previous caesarean scars, of which 10 occurred in women with previous four or more caesarean sections. In 12 cases (27%), uterine rupture occurred due to oxytocin; PGE2 and oxytocin were used in 3 of these 12 cases. Two (4.5%) ruptures occurred due to non-removal of cervical cerclage during labor. Two (4.5%) primigravidae ruptured their uterus following road traffic accident, resulting in maternal and fetal deaths. Malpresentation in labor resulted in eight (18%) ruptures. Rupture occurred at the fundus in 10 cases and in the lower segment in the remaining 34. Fetal heart abnormalities were observed in all cases in which the uterus ruptured during labor. Abdominal hysterectomy was performed in 20 cases (45%) of which 13 were subtotal and 7 (10%) were total. Of the remaining 24 (55%) patients, 10 had suture repair and in addition 14 patients underwent hypogastric artery ligation. Later, 22/24 (92%) women became pregnant. Twenty (91%) were delivered by planned caesarean section. There were no maternal or fetal complications. The remaining two women had previous classical scar, undetected malpresentation, and sparse antenatal care. Their uteri ruptured spontaneously at 32 and 35 weeks at home. They died intra-operatively due to intractable hemorrhage along with their fetus. CONCLUSION: In the previous caesarean section, the indiscriminate use of oxytocin and malpresentation are the risk factors for uterine rupture. Child birth after uterine rupture is not to be recommended routinely. Most women with a previous uterine rupture with meticulous tertiary level antenatal care had a favorable outcome in subsequent pregnancies.

Transport kinetics of cisplatin in the perfused human placental lobule in vitro.

OBJECTIVE: Platinum-containing drugs are used extensively in the treatment of various malignancies in humans. Data are scarce on the maternal-fetal transport characteristics in humans of one such widely used drug, cisplatin, and this prompted us to study its transport characteristics in the human placenta in vitro. METHODS: Placentae from normal pregnancies were collected after delivery. Cisplatin, along with antipyrine as an internal reference marker, was injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution, was used as the perfusate. The concentration of cisplatin in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was quantified by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of cisplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.49 +/- 0.02, 1.23 +/- 0.03, 2.41 +/- 0.04, 3.67 +/- 0.03, and 4.48 +/- 0.07 minutes in 12 perfusions, while corresponding rates for antipyrine, for above mentioned efflux fractions averaged 0.51 +/- 0.01, 1.26 +/- 0.05, 2.52 +/- 0.01, 3.78 +/- 0.01, and 4.52 +/- 0.01 minutes, respectively. Cisplatin transport rates averaged 0.97, 0.97, 0.96, 0.97, and 0.99 times the antipyrine reference value. Analysis of variance (ANOVA) did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of cisplatin, expressed as a fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.6 +/- 2.01% of injected bolus dose, representing 13.10% of reference marker value. The Student's t-test showed cisplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, and elimination rate of study and reference substances also varied significantly (p < 0.05). CONCLUSIONS: We report for the first time that cisplatin transport is negligible in the human placenta at term. It is reasonable to assume that the risk for the neonate from cisplatin use in pregnancy is minimal when it is used in emergency clinical situations.