The Association between Antenatal Tea Drinking and Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis.

Several adverse maternal outcomes have been linked to the excessive consumption of caffeine during pregnancy. Tea is an important source of caffeine. Hypertensive disorders of pregnancy (HDP) are common pregnancy complications with unfavorable maternal and fetal complications. This study aimed to investigate the relationship between antenatal tea drinking and HDP using a meta-analysis of available evidence. We systematically retrieved eligible studies before computing the pooled odds ratio (OR) and 95% confidence interval (CI) of HDP for women who reported the highest versus the lowest frequencies of antenatal tea drinking. We used the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. The results showed that the highest frequencies of antenatal tea drinking were associated with increased odds of HDP (pooled OR = 1.16, 95% CI: 1.01, 1.33). We identified no signs of heterogeneity across studies (I2 = 0.0% and p-heterogeneity = 0.498) or publication bias (z = 0.791 and p-publication bias = 0.429). When the outcome was limited to (pre-)eclampsia, the association became statistically non-significant (pooled OR = 1.28, 95% CI: 0.86, 1.89, I2 = 0.0%, and p-heterogeneity = 0.751). In conclusion, our results indicated that the highest frequency of antenatal tea drinking was positively associated with HDP. Pregnant women should be advised against excessive tea consumption. Still, future prospective cohort studies, considering the effects of different tea types and caffeine content, are needed to confirm our conclusions.

Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus.

BACKGROUND: The annual prevalence of gestational diabetes mellitus-characterized by an increase in blood glucose in pregnant women-has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. METHODS: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. RESULTS: The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. CONCLUSIONS: Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life.

Clinical practice guidelines for neonatal hypoxic-ischemic encephalopathy: A systematic review using the appraisal of guidelines for research and evaluation (AGREE) II instrument.

Background and Objective: To systematically review, critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal hypoxic ischemic encephalopathy (HIE), and map their recommendations. Data Sources: CPG databases (GIN, ECRI, NICE, SIGN, DynaMed), Bibliographic databases (PubMed, Embase, CINAHL), and related specialized professional societies (e.g., AAP, CPS, BAPM, RCPCH, and SNS). Study Selection: Original de-novo developed evidence-based CPGs for HIE, group authorship, Arabic or English languages, and international or national scope. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and Johnston et al methodological guide. Data Extraction: Quality assessment of the included HIE CPGs by the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) Instrument and report their characteristics, AGREE II ratings, and recommendations. Data Synthesis: Our search retrieved 2,489 citations, of which two recent HIE CPGs were eligible and appraised: Canadian Paediatric Society (CPS) and Queensland Maternity and Neonatal Services (QMN). The overall assessment of the QMN CPG was superior (83%). Domain 1 (Scope & Purpose) scored (47%, 63%), Domain 2 (Stakeholder Involvement) (72%, 39%), Domain 3 (Rigour of Development) (48%, 43%), Domain 4 (Clarity & Presentation) (100%, 96%), Domain 5 (Applicability) (59%, 9%), and Domain 6 (Editorial Independence) (67%, 17%) for the QMN and CPS CPGs respectively. All appraisers recommended the QMN CPG for use in practice. Conclusion: The methodological quality of the QMN CPG was superior with the relevant recommendations for its use in neonatal practice. Limitations: limited to Arabic and English languages. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=258291, identifier: CRD42021258291.

Association of health and lifestyle factors with uterine fibroids among Saudi women: A case-control study.

Objectives: The objective of this study was to measure the association between uterine fibroids (UFs) and several risk factors (parity, miscarriage, diabetes, hypertension, physical activity, smoking, family history of UF and contraceptive pill use) among Saudi women. Methods: A case-control study was conducted in 478 women at two medical centers in Riyadh. Cases were confirmed by ultrasound. Demographic and risk factor information was collected from interviews and medical records. The prevalence of risk factors was calculated with 95% confidence interval (CI). Unconditional logistic regression analysis was used to measure the associations between UFs and the risk factors. Results: More than half the participants were obese. The average body mass index (BMI) was 31.2 (±6.81) for cases and 29.4 (±7.02) for controls. Women 40 years or older had four times the odds of UFs than women younger than 40 years (adjusted odds ratio [AOR] = 4.24, 95% CI = 2.63, 6.85). Having a family history of UFs was associated with 69% greater odds of UFs (AOR = 1.69, 95% CI = 1.02, 2.81). Being obese was associated with 74% greater odds of UFs (AOR = 1.74, 95% CI = 1.00, 2.59), whereas previous live births decreased the odds of UFs by 62% (AOR = 0.38, 95% CI = 0.19, 0.75). Conclusions: This study identified risk factors associated with UFs in the Saudi population. Age over 40 years, obesity and a family history of UFs are important risk factors for UF, whereas parity appears to be protective against UF development in Saudi women. Early recognition of these risk factors is important to prevent UF complications.

Racial and Ethnic Disparities in the Perinatal Health of Infants Conceived by ART.

BACKGROUND AND OBJECTIVES: Although racial and ethnic disparities in adverse birth outcomes have been well documented, it is unknown whether such disparities diminish in women who use medically assisted reproduction (MAR). We examined differences in the association between maternal race and ethnicity and adverse birth outcomes among women who conceived spontaneously and those who used MAR, including assisted reproduction technology (ART), eg, in-vitro fertilization, and also non-ART MAR, eg, fertility drugs. METHODS: We conducted a population-based retrospective cohort study using data on all singleton births (N = 7 545 805) in the United States from 2016 to 2017. The outcomes included neonatal and fetal death, preterm birth, and serious neonatal morbidity, among others. Modified Poisson regression was used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) and to assess the interactions between race and ethnicity and mode of conception. RESULTS: Overall, 93 469 (1.3%) singletons were conceived by MAR. Neonatal mortality was twofold higher among infants of non-Hispanic Black versus non-Hispanic White women in the spontaneous-conception group (aRR = 1.9, 95% CI: 1.8-1.9), whereas in the ART-conception group, neonatal mortality was more than fourfold higher in infants of non-Hispanic Black women (aRR = 4.1, 95% CI: 2.9-5.9). Racial and ethnic disparities between Hispanic versus non-Hispanic White women were also significantly larger among women who conceived using MAR with regard to preterm birth (<34 weeks) and perinatal mortality. CONCLUSIONS: Compared to women who conceived spontaneously, racial and ethnic disparities in adverse perinatal outcomes were larger in women who used MAR. More research is needed to identify preventive measures for reducing risks among vulnerable women who use medically assisted reproduction.

Severe Maternal Morbidity and Maternal Mortality Associated with Assisted Reproductive Technology.

OBJECTIVE: To assess the association between use of assisted reproductive technologies (ART) and severe maternal morbidity and maternal mortality (SMM). METHODS: We carried out a cohort study that included all hospital deliveries at ≥20 weeks gestation in Canada (excluding Québec) between April 2009 and March 2018. Outcomes of interest included composite SMM and SMM types (e.g., severe preeclampsia, HELLP syndrome, and eclampsia; severe hemorrhage; acute renal failure). Multivariable regression was used to estimate crude and adjusted rate ratios (RR and aRR) and 95% confidence intervals (CI). RESULTS: The study included 2 535 056 women, of whom 72 023 (2.8%) delivered following the use of ART. The composite SMM rate for women who used ART was 34.7 per 1000 deliveries (95% CI 33.0-36.0) versus 11.5 per 1000 deliveries (95% CI 11.4-11.6) for women who did not use ART (RR 3.01; 95% CI 2.89-3.14). ART use was associated with SMM types such as severe preeclampsia, HELLP syndrome, and eclampsia (RR 3.50; 95% CI 3.27-3.73), severe hemorrhage (RR 3.58, 95% CI 3.27-3.92), and acute renal failure (RR 6.79; 95% CI 5.78-7.98). Associations between ART and composite SMM were attenuated but remained elevated after adjusting for maternal characteristics (aRR 2.34; 95% CI 2.24-2.45). Women who used ART and had a multi-fetal pregnancy had a 4.7 times higher rate of composite SMM compared with women who did not use ART and delivered singletons. CONCLUSION: Women who deliver following the use of ART have increased risks of SMM and require counselling that includes mention of the lower risks of SMM associated with ART-conceived singleton pregnancy.

Impact of COVID-19 pandemic on urology residency training.

CONTEXT: The COVID-19 pandemic has led a lot of countries worldwide to go on lockdown. Potential collateral damage is the impact of residency. AIMS: The aim of this study is to assess the impact of COVID-19 pandemic on urology training aspects, study habits of residents, and their awareness and training regarding COVID-19. SETTINGS AND DESIGN: A questionnaire aiming to assess the impact of COVID-19 pandemic on different urology training aspects. The questionnaire was sent to all urology residents under the Saudi Commission for Health Specialties (SCFHS) programs. SUBJECTS AND METHODS: Urology residents under SCFHS programs, excluding 1st-year residents. The questionnaire included the following sections: demographic data, studying habits during the pandemic, involvement in training before the pandemic, involvement in training during the pandemic, and training related to COVID-19. STATISTICAL ANALYSIS USED: Using the SPSS software, frequencies of all data were calculated, and a Wilcoxon-signed rank test was done to assess the change in ordinal data. RESULTS: A total of 77 residents completed the survey (38% response rate). Most residents (40.5%) reported that they "strongly agree" with the statement that they have more time for reading. There has been a decrease in on-call duties, outpatient visits, diagnostic procedures, endoscopic surgeries urology, minimally-invasive surgeries, and major open surgeries in comparison to before the pandemic, with a decrease in mean scores in all domains, especially in diagnostic procedures. CONCLUSIONS: There has been a decrease in residents' involvement in all training domains, and this has been similar to the results of other studies. E-learning sources, during these times, present themselves as a valuable source to compensate for what has been missed in training.

Incidence and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm and term gestation: a population-based study.

BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.

Maternal Mortality in the United States: Recent Trends, Current Status, and Future Considerations.

Rigorous studies carried out by the National Center for Health Statistics show that previously reported increases in maternal mortality rates in the United States were an artifact of changes in surveillance. The pregnancy checkbox, introduced in the revised 2003 death certificate and implemented by the states in a staggered manner, resulted in increased identification of maternal deaths and in reported maternal mortality rates. This Commentary summarizes the findings of the National Center for Health Statistics reports, describes temporal trends and the current status of maternal mortality in the United States, and discusses future concerns. Although the National Center for Health Statistics studies, based on recoding of death certificate information (after excluding information from the pregnancy checkbox), showed that crude maternal mortality rates did not change significantly between 2002 and 2018, age-adjusted analyses show a temporal reduction in the maternal mortality rate (21% decline, 95% CI 13-28). Specific causes of maternal death, which were not affected by the pregnancy checkbox, such as preeclampsia, showed substantial temporal declines. However, large racial disparities continue to exist: Non-Hispanic Black women had a 2.5-fold higher maternal mortality rate compared with non-Hispanic White women in 2018. This overview of maternal mortality underscores the need for better surveillance and more accurate identification of maternal deaths, improved clinical care, and expanded public health initiatives to address social determinants of health. Challenges with ascertaining maternal deaths notwithstanding, several causes of maternal death (unaffected by surveillance artifacts) show significant temporal declines, even though there remains substantial scope for preventing avoidable maternal death and reducing disparities.

Validity and reliability of the Arabic version of Muller's prenatal attachment inventory.

PURPOSE: Maternal fetal attachment (MFA) is the bond between the mother and her unborn baby. Presently no tools measuring MFA are available in Arabic. The aim of this study was to translate Muller's Prenatal Attachment Inventory (PAI) from English to Arabic, examine the cultural appropriateness of this tool, and test its psychometric properties with pregnant women in an Arab country. MATERIALS AND METHODS: The PAI was translated from English into Arabic using the Universal Translation Approach (modified tool) and assessed for content validity. During this process four additional items were identified for measurement relevance and cultural acceptability resulting in the revised tool. The psychometric properties of the modified and revised tools were assessed after 250 pregnant Arab women completed the PAI. Factor analysis was conducted to assess construct validity, while reliability was assessed using Cronbach's alpha coefficient. RESULTS: Both tools were shown to be unidimensional with excellent reliability (Cronbach's alpha = 0.88 for the modified tool and 0.89 for the revised tool). Nulliparity, planning to breastfeed the baby, feeling fetal movements, and downloading a smartphone app to follow the baby's growth were associated with increased MFA in the PAI, while only planning to breastfeed the baby, feeling fetal movements, and downloading a smartphone app to follow the baby's growth were associated with increased MFA in the revised PAI. CONCLUSION: The Arabic version of the PAI is a culturally appropriate tool to measure MFA amongst Arabic-speaking women.

Quality assessment of evidence-based clinical practice guidelines for the management of pregnant women with sickle cell disease using the AGREE II instrument: a systematic review.

BACKGROUND: The management of pregnant women with sickle cell disease (SCD) poses a major challenge for maternal healthcare services owing to the potential for complications associated with morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on the positive outcomes of appropriate healthcare. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnant women. METHODS: Clinical questions were identified and the relevant CPG and bibliographic databases were searched and screened for eligible CPGs. Each CPG was appraised by four independent appraisers using the AGREE II Instrument. Inter-rater analysis was conducted. RESULTS: Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health and Care Excellence (NICE), and Royal College of Obstetricians and Gynaecologists (RCOG). Among them, the overall assessments of three CPGs (NICE, RCOG, NHLBI) scored greater than 70%; these findings were consistent with the high scores in the six domains of AGREE II, including:[1] scope and purpose,[2] stakeholder involvement,[3] rigor of development,[4] clarity of presentation,[5] applicability, and [6] editorial independence domains. Domain [3] scored (90%, 73%, 71%), domain [5] (90%, 46%, 47%), and domain [6] (71%, 77%, 52%) for NICE, RCOG, and NHLBI, respectively. Overall, the clinical recommendations were not significantly different between the included CPGs. CONCLUSIONS: Three evidence-based CPGs presented superior methodological quality. NICE demonstrated the highest quality followed by RCOG and NHLBI and all three CPGs were recommended for use in practice.

Saudi Society of Maternal-Fetal Medicine guidance on pregnancy and coronavirus disease 2019.

[No Abstract Available]    Saudi Med J 2020; Vol. 41 (8): 779-790doi: 10.15537/smj.2020.8.25222 How to cite this article:Yaser A. Faden, Nadia A. Alghilan,  Samiha H. Alawami, Eman S. Alsulmi, Hythem A. Alsum, Yasir A. Katib, Yasser S. Sabr, Fadwah H. Tahir, Nabeel S. Bondagji. Saudi Society of Maternal-Fetal Medicine guidance on pregnancy and coronavirus disease 2019. Saudi Med J 2020; Vol. 41 (8): 779-790. doi: 10.15537/smj.2020.8.25222.

Prevalence of symptoms and risk of obstructive sleep apnea in Saudi pregnant women.

BACKGROUND: This case-control study aimed to assess the prevalence of symptoms and risk of obstructive sleep apnea (OSA) among Saudi pregnant women. METHODS: The study included consecutive Saudi pregnant women attending the antenatal service between July 2015 and December 2016. Pregnant women were compared with an age-matched group of nonpregnant women. OSA symptoms and risk were assessed using a validated Arabic version of the Berlin questionnaire (BQ). RESULTS: The study included 742 pregnant women and 742 age-matched nonpregnant women. At the time of the survey, 8.2% were in the first trimester; 33.4% in the second trimester; and 58.4%in third trimester. Snoring was reported by 14% of pregnant women, and 5% reported breathing pauses during sleep. Based on the BQ stratification for risk of OSA, 19.3% of pregnant women and 16.6% of the control group were at high risk for OSA. A comparison between the high OSA-risk and low OSA-risk pregnant women revealed that the pregnant women in high risk group were older (30.9 ± 5.9 years vs. 29 ± 5.4 years, P = 0.001), had a higher body mass index (BMI) (34.3 ± 5.2 kg/m2 vs. 28.7 ± 5.8 kg/m2, P < 0.001), and higher parity (1.9 ± 2 vs. 1.5 ± 1.7, P = 0.020). A multivariate logistic regression analysis revealed the following independent variables, BMI (odds ratio [OR] 1.173 [95% confidence interval [CI] 1.129-1.219],P < 0.001), pregnancy-induced hypertension (OR 7.85 [95% CI 1.691-36.447], P = 0.013), and the presence of restless legs syndrome (OR 2.209 [95% CI 1.332-3.279],P < 0.001). CONCLUSIONS: OSA symptoms and risk were relatively common among Saudi pregnant women. Increasing the awareness among physicians about this association is essential to improve early detection of the disorder.

Systematic review and meta-analysis of the effectiveness of pre-pregnancy care for women with diabetes for improving maternal and perinatal outcomes.

BACKGROUND: Pre-gestational diabetes mellitus is associated with increased risk of maternal and perinatal adverse outcomes. This systematic review was conducted to evaluate the effectiveness and safety of pre-conception care (PCC) in improving maternal and perinatal outcomes. METHODS: Databases from MEDLINE, EMBASE, WEB OF SCIENCE, and Cochrane Library were searched, including the CENTRAL register of controlled trials, and CINHAL up until March 2019, without any language restrictions, for any pre-pregnancy care aiming at health promotion, glycemic control, and screening and treatment of diabetes complications in women with type I or type II pre-gestational diabetes. Trials and observational studies were included in the review. Newcastle-Ottawa scale and the Cochrane collaboration methodology for data synthesis and analysis were used, along with the GRADE tool to evaluate the body of evidence. RESULTS: The search identified 8500 potentially relevant citations of which 40 reports of 36 studies were included. The meta-analysis results show that PCC reduced congenital malformations risk by 71%, (Risk ratio (RR) 0.29; 95% CI: 0.21-0.40, 25 studies; 5903 women; high-certainty evidence). The results also show that PCC may lower HbA1c in the first trimester of pregnancy by an average of 1.27% (Mean difference (MD) 1.27; 95% CI: 1.33-1.22; 4927 women; 24 studies, moderate-certainty evidence). Furthermore, the results suggest that PCC may lead to a slight reduction in the risk of preterm delivery of 15%, (RR 0.85; 95% CI: 0.73-0.99; nine studies, 2414 women; moderate-certainty evidence). Moreover, PCC may result in risk reduction of perinatal mortality by 54%, (RR 0.46; 95% CI: 0.30-0.73; ten studies; 3071 women; moderate-certainty evidence). There is uncertainty about the effects of PCC on the early booking for antenatal care (MD 1.31; 95% CI: 1.40-1.23; five studies, 1081 women; very low-certainty evidence) and maternal hypoglycemia in the first trimester, (RR 1.38; 95% CI: 1.07-1.79; three studies; 686 women; very low- certainty evidence). In addition, results of the meta-analysis indicate that PCC may lead to 48% reduction in the risk of small for gestational age (SGA) (RR 0.52; 95% CI: 0.37-0.75; six studies, 2261 women; moderate-certainty evidence). PCC may reduce the risk of neonatal admission to intensive care unit (NICU) by 25% (RR 0.75; 95% CI: 0.67-0.84; four studies; 1322 women; moderate-certainty evidence). However, PCC may have little or no effect in reducing the cesarean section rate (RR 1.02; 95% CI: 0.96-1.07; 14 studies; 3641 women; low-certainty evidence); miscarriage rate (RR 0.86; 95% CI: 0.70-1.06; 11 studies; 2698 women; low-certainty evidence); macrosomia rate (RR 1.06; 95% CI: 0.97-1.15; nine studies; 2787 women, low-certainty evidence); neonatal hypoglycemia (RR 0.93; 95% CI: 0.74-1.18; five studies; 880 women; low-certainty evidence); respiratory distress syndrome (RR 0.78; 95% CI: 0.47-1.29; four studies; 466 women; very low-certainty evidence); or shoulder dystocia (RR 0.28; 95% CI: 0.07-1.12; 2 studies; 530 women; very low-certainty evidence). CONCLUSION: PCC for women with pre-gestational type 1 or type 2 diabetes mellitus is effective in improving rates of congenital malformations. In addition, it may improve the risk of preterm delivery and admission to NICU. PCC probably reduces maternal HbA1C in the first trimester of pregnancy, perinatal mortality and SGA. There is uncertainty regarding the effects of PCC on early booking for antenatal care or maternal hypoglycemia during the first trimester of pregnancy. PCC has little or no effect on other maternal and perinatal outcomes.

Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features.

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15.