scholarly journals Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

2022 ◽  
Vol 12 ◽  
Author(s):  
José Timsit ◽  
Cécile Ciangura ◽  
Danièle Dubois-Laforgue ◽  
Cécile Saint-Martin ◽  
Christine Bellanne-Chantelot

Heterozygous loss-of-function variants of the glucokinase (GCK) gene are responsible for a subtype of maturity-onset diabetes of the young (MODY). GCK-MODY is characterized by a mild hyperglycemia, mainly due to a higher blood glucose threshold for insulin secretion, and an up-regulated glucose counterregulation. GCK-MODY patients are asymptomatic, are not exposed to diabetes long-term complications, and do not require treatment. The diagnosis of GCK-MODY is made on the discovery of hyperglycemia by systematic screening, or by family screening. The situation is peculiar in GCK-MODY women during pregnancy for three reasons: 1. the degree of maternal hyperglycemia is sufficient to induce pregnancy adverse outcomes, as in pregestational or gestational diabetes; 2. the probability that a fetus inherits the maternal mutation is 50% and; 3. fetal insulin secretion is a major stimulus of fetal growth. Consequently, when the fetus has not inherited the maternal mutation, maternal hyperglycemia will trigger increased fetal insulin secretion and growth, with a high risk of macrosomia. By contrast, when the fetus has inherited the maternal mutation, its insulin secretion is set at the same threshold as the mother’s, and no fetal growth excess will occur. Thus, treatment of maternal hyperglycemia is necessary only in the former situation, and will lead to a risk of fetal growth restriction in the latter. It has been recommended that the management of diabetes in GCK-MODY pregnant women should be guided by assessment of fetal growth by serial ultrasounds, and institution of insulin therapy when the abdominal circumference is ≥ 75th percentile, considered as a surrogate for the fetal genotype. This strategy has not been validated in women with in GCK-MODY. Recently, the feasibility of non-invasive fetal genotyping has been demonstrated, that will improve the care of these women. Several challenges persist, including the identification of women with GCK-MODY before or early in pregnancy, and the modalities of insulin therapy. Yet, retrospective observational studies have shown that fetal genotype, not maternal treatment with insulin, is the main determinant of fetal growth and of the risk of macrosomia. Thus, further studies are needed to specify the management of GCK-MODY pregnant women during pregnancy.

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
G M A Elbishry ◽  
R R Ali ◽  
R T Ramadan

Abstract Background Fetal Growth Restriction (FGR) is the one of largest contributing factor to perinatal morbidity in non-anomalous fetuses and is associated with an increased risk of stillbirth, neonatal death and short and long-term complications. Fetal growth restriction (FGR) is defined as an estimated fetal weight and/or abdominal circumference (AC) is less than the10th percentile. In order to avoid these adverse outcomes, the management of pregnancies with FGR involves close monitoring of fetal well-being and early delivery when necessary. Screening for FGR during pregnancy is thus a central component of prenatal care, as highlighted in recent national guidelines, first-line tools include risk factor assessment at the beginning and during pregnancy. Hence, in this study we evaluated the maternal risk factors and diagnosis-delivery intervals and perinatal outcomes in FGR. Aim To determine the effect of specific antenatal FGR risk factors on fetal growth trajectory and the outcomes using threshold of estimated fetal weight (EFW) and abdominal circumference (AC) <10th percentile. Methods Prospective observational analytical study was conducted in a tertiary care hospital in Cairo, Egypt on 100 pregnant women with documented fetal growth restriction attended Ain Shams University hospital over a period of 1 year and eight months. All fetuses considered as growth restrictions. Fetuses with multiple pregnancy, congenital malformation, chromosomal abnormality, and premature rupture of membrane were. Socio-demographic, maternal risk, Diagnosis- delivery interval in FGR and neonatal morbidities were studied. Results This study included 100 pregnant women with documented FGR fetuses, the mean maternal age at diagnosis was 28.6±2.7 years, the mean pregnant women weight at diagnosis was 72.7±5.1 (kg) with BMI range 25.6–29.8 (kg/m2) and their pregnancy weight gain was 12.0–25.0 (kg), 50 women used to consume caffeine more than 200 mg/day, and the percentage of nicotine exposure was 22% of total studied pregnants, 19 % were passive smokers and 3% of them were active. 73% were multigravida and the rest were primi-gravida, the mean inter-pregnancy interval was 17.3±4.7 months. Obstetric history of Previous placental mediated diseases included (prior FGR, previous intrauterine fetal death (IUFD), Pre-eclampsia and un-explained antepartum hemorrhage) were distributed as follows 16.0%, 6.0%, 12.0% and 2.0% respectively. Also we found 2.0% had an in vitro fertilization (IVF) and 26 women got regular antenatal care (ANC). At the end of our study 45% of fetuses were delivered at completed 37 weeks and 55% showed pre-term delivery (before 37 weeks). 95% of total were delivered by caesarean section. The indications for caesarean section were different. So, among 100 FGR fetuses, 35 fetus had abnormal Doppler pattern which considered the main indication for termination of pregnancy, the most frequent one was absent/reversed ductus venosus Doppler which was the cause of preterm immediate caesarean section in 4 of fetuses. We also found 2 fetuses with also absent/reversed EDV but with abnormal CTG, we found 20 fetuses with PI > 2SD with preserved EDV and completed 37 weeks, 13% had non-reactive non-stress test (NST) necessitating imminent delivery, also 3 fetuses with absent EDV > 34 weeks while only one fetus with reversed EDV >32 weeks. We found 1 fetus with static growth over 3 weeks during our follow up, also we discovered 1 pregnant women who developed accidental hemorrhage with placental separation and other 3 women developed sever pre-eclampsia who underwent emergency caesarean section after controlling their condition. Conclusion FGR is associated with sociodemographic status and various medical conditions. Analysis of various maternal and familial risk factors is an integral part of in-utero fetal surveillance to identify impending fetal hypoxia. Appropriate management should be offered to these FGR fetuses, is optimizing the timing of delivery to improve perinatal health in FGR.


2017 ◽  
Vol 216 (1) ◽  
pp. S105-S106
Author(s):  
Lorene A. Temming ◽  
Fayola F. Fears ◽  
Omar M. Young ◽  
Molly J. Stout ◽  
Methodius G. Tuuli ◽  
...  

2017 ◽  
Vol 4 (6) ◽  
pp. 2136
Author(s):  
Sathish Kumar S. ◽  
Anandhi A. ◽  
Luke Ravi Chelliah ◽  
Karthick A. R.

Background: Gestational diabetes mellitus represents a metabolically altered fetal environment due to an increased maternal supply of carbohydrates. It leads to fetal hyperinsulinemia and stimulates insulin-sensitive tissue, predominantly of the abdomen, resulting in increased fetal growth and delivering large-for-gestational-age newborns. Implications of fetal hyperinsulinemia reach far beyond delivery. Children of mothers with diabetes in pregnancy are predisposed to develop obesity and glucose intolerance through a non-genetic “fuel-mediated” mechanism. The objective of the present study was to study the “fetal growth pattern at different periods of pregnancy complicated by diabetes” and to identify the factors that influence the fetal growth pattern in pregnancy complicated by diabetesMethods: 69 pregnant women with diabetes and 34 pregnant women without diabetes were included in the study by random sampling. Maternal parameters such as age, parity, height, weight at registration, and weight gain during pregnancy, BMI at the time of registration of pregnancy and at the time of delivery, detailed diabetic profile and management including meal plan, insulin administration and dosage were recorded. The fetuses were monitored for Biparietal diameter, abdomen circumference, femur length by 2 ultrasound examinations, one at 18-22 weeks and another at 28-32 weeks were performed. Soon after delivery, sex, gestational age, birth weight, length, head circumference and chest circumference of the newborn were recorded and infants were classified as LGA/SGA/AGA.Results: Maternal age, parity, BMI at the time of delivery and maternal weight gain had significant influence on the birth weight. The abdominal circumference of the fetus detected at 18-20 and 28-32 ultrasound scans had a very significant correlation with neonatal mean birth weight percentile. Conclusions: Not all babies born to diabetic mothers are macrosomic. SGA babies were not uncommon in pregnancies with diabetes especially in those who did not have significant micro vasculopathy. Maternal nutrition plays a significant key role in determining birth weight of babies even in pregnancies complicated by diabetes.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Fanghua Shen ◽  
Hongdao Lv ◽  
Yun Shi ◽  
Sandy Lau ◽  
Fang Guo ◽  
...  

Abstract To date there is no effective treatment for pregnancies complicated by fetal growth restriction (FGR). Salvia miltiorrhiza, a traditional Chinese herb has been shown to promote blood flow and improve microcirculatory disturbance. In this pilot study, we evaluated whether S. miltiorrhiza can potentially become a possible therapy for FGR. Nineteen pregnant women with FGR were treated with S. miltiorrhiza and ATP supplementation for an average of 7 days, and 17 cases received ATP supplementation as controls. The estimated fetal weights (EFWs) were measured by ultrasound after treatment, and the birthweights were recorded after birth. After treatment with S. miltiorrhiza, 7 (37%) FGR cases showed an increase in EFW to above the 10th percentile, compared with 4 (23%) FGR cases in controls (odds ratio: 1.896, 95% confidence limits (CLs): 0.44–8.144). At delivery, 10 (53%) FGR cases in the treatment group delivered babies with a birthweight above the 10th percentile, compared with 6 (35%) FGR cases in the control group (odds ratio: 2.037, 95% CL: 0.532–7.793); 80 or 64% FGR cases in the treatment group showed an increase in fetal abdominal circumference (AC) or biparietal diameter (BPD) above the 10th percentile before delivery. While 44 or 30% FGR cases in the control group showed an increase in AC or BPD. No improvement of head circumference (HC) or femur length (FL) was seen. These pilot data suggest the need for multicenter randomized clinical trials on the potential of S. miltiorrhiza to improve perinatal outcome in pregnant women complicated by FGR.


1980 ◽  
Vol 95 (3) ◽  
pp. 372-375 ◽  
Author(s):  
B. J. Burke ◽  
R. J. Sherriff

Abstract. Residual insulin secretion, reflected by the presence of C-peptide in serum and urine, has been demonstrated in 5 of 10 insulin-requiring diabetics of less than 10 years' duration tested. The C-peptide response, in the C-peptide secretors, showed a significant increase in both serum and urine after 4 weeks' treatment with 15 mg glibenclamide daily in addition to their usual insulin regime although no beneficial effects in metabolic control were detected. It is suggested that glibenclamide might be a useful adjunct to insulin therapy in insulinrequiring diabetics who still secrete C-peptide.


Author(s):  
Yakubova D.I.

Objective of the study: Comprehensive assessment of risk factors, the implementation of which leads to FGR with early and late manifestation. To evaluate the results of the first prenatal screening: PAPP-A, B-hCG, made at 11-13 weeks. Materials and Methods: A retrospective study included 110 pregnant women. There were 48 pregnant women with early manifestation of fetal growth restriction, 62 pregnant women with late manifestation among them. Results of the study: The risk factors for the formation of the FGR are established. Statistically significant differences in the indicators between groups were not established in the analyses of structures of extragenital pathology. According to I prenatal screening, there were no statistical differences in levels (PAPP-A, b-hCG) in the early and late form of FGR.


2019 ◽  
Vol 15 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Harpriya Kaur ◽  
Delf Schmidt-Grimminger ◽  
Baojiang Chen ◽  
K.M. Monirul Islam ◽  
Steven W. Remmenga ◽  
...  

Background: Pregnancy may increase the risk of Human Papillomavirus (HPV) infection because of pregnancy induced immune suppression. The objective of this study was to use a large population-based dataset to estimate the prevalence of HPV infection and its association with adverse outcomes among pregnant women. Methods: We analyzed Pregnancy Risk Monitoring System data from 2004-2011 (N=26,085) to estimate the self-reported HPV infection. Survey logistic procedures were used to examine the relationship between HPV infection and adverse perinatal outcomes. Results: Approximately 1.4% of women were estimated to have HPV infection during their pregnancy. The prevalence of adverse outcomes in this sample was preterm birth (8.4%), preeclampsia (7.5%), low birth weight (6.3%) and premature rupture of membranes (2.8%). Compared to women without HPV infection, HPV infection positive women were much more likely to have had other infections such as chlamydia (9.23% vs. 2.12%, p-value <.0001), Group B Strep (21.7% vs. 10.04%, p-value <.0001), and herpes (7.17% vs. 1.07%, p-value <.0001). After adjusting for other risk factors including other infections, HPV infection was significantly associated with low birth weight (OR: 1.94, 95% CI: 1.14-3.30). Conclusion: The study indicated a potential association between HPV infection and low birth weight. Because pregnant women with HPV infection are at higher risk of other infections, future research may focus on the roles of co-infection in the development of adverse perinatal effects.


Author(s):  
Leah Zilversmit Pao ◽  
Emily W. Harville ◽  
Jeffrey K. Wickliffe ◽  
Arti Shankar ◽  
Pierre Buekens

Metals, stress, and sociodemographics are commonly studied separately for their effects on birth outcomes, yet often jointly contribute to adverse outcomes. This study analyzes two methods for measuring cumulative risk to understand how maternal chemical and nonchemical stressors may contribute to small for gestational age (SGA). SGA was calculated using sex-specific fetal growth curves for infants of pregnant mothers (n = 2562) enrolled in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. The exposures (maternal lead, mercury, cadmium, Cohen’s perceived stress, Edinburgh depression scores, race/ethnicity, income, and education) were grouped into three domains: metals, psychosocial stress, and sociodemographics. In Method 1 we created cumulative risk scores using tertiles. Method 2 employed weighted quantile sum (WQS) regression. For each method, logistic models were built with three exposure domains individually and race/ethnicity, adjusting for age, parity, pregnancy weight gain, and marital status. The adjusted effect of overall cumulative risk with three domains, was also modeled using each method. Sociodemographics was the only exposure associated with SGA in unadjusted models ((odds ratio) OR: 1.35, 95% (confidence interval) CI: 1.08, 1.68). The three cumulative variables in adjusted models were not significant individually, but the overall index was associated with SGA (OR: 1.17, 95% CI: 1.02, 1.35). In the WQS model, only the sociodemographics domain was significantly associated with SGA. Sociodemographics tended to be the strongest risk factor for SGA in both risk score and WQS models.


2021 ◽  
Vol 224 (2) ◽  
pp. S263
Author(s):  
Aaron Dom ◽  
Lisa Gray ◽  
Zi Qi Liew ◽  
J. Christopher Glantz ◽  
Katherine Rogg ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Ren ◽  
Zhe Qiang ◽  
Yuan-yuan Li ◽  
Jun-na Zhang

Abstract Background Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human chorioamnionitis. The present study analyzed the impact of GBS infection and histological chorioamnionitis (HCA) on pregnancy outcomes and the diagnostic value of various biomarkers. Methods Pregnant women were grouped according to GBS infection and HCA detection. Perinatal and neonatal adverse outcomes were recorded with a follow-up period of 6 weeks. The white blood cell count (WBC), neutrophil ratio, and C-reactive protein (CRP) level from peripheral blood and soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels from cord blood were assessed. Results A total of 371 pregnant women were included. Pregnant women with GBS infection or HCA had a higher risk of pathological jaundice and premature rupture of membranes and higher levels of sICAM-1, IL-8, and TNF-α in umbilical cord blood. Univariate and multivariate regression analysis revealed that sICMA-1, IL-8, TNF-α, WBC, and CRP were significantly related to an increased HCA risk. For all included pregnant women, TNF-α had the largest receiver operating characteristic (ROC) area (area: 0.841; 95% CI: 0.778–0.904) of the biomarkers analyzed. TNF-α still had the largest area under the ROC curve (area: 0.898; 95% CI: 0.814–0.982) for non-GBS-infected pregnant women, who also exhibited a higher neutrophil ratio (area: 0.815; 95% CI: 0.645–0.985) and WBC (area: 0.849; 95% CI: 0.72–0.978), but all biomarkers had lower value in the diagnosis of HCA in GBS-infected pregnant women. Conclusion GBS infection and HCA correlated with several perinatal and neonatal adverse outcomes. TNF-α in cord blood and WBCs in peripheral blood had diagnostic value for HCA in non-GBS-infected pregnant women but not GBS-infected pregnant women.


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