Browsing by Author "Kaplan, Yusuf C."

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Citation - WoS: 27
Citation - Scopus: 28
Major Malformations Risk Following Early Pregnancy Exposure To Metformin: a Systematic Review and Meta-Analysis
(Bmj Publishing Group, 2023) Abolhassani, Nazanin; Winterfeld, Ursula; Kaplan, Yusuf C.; Jaques, Cecile; Minder Wyssmann, Beatrice; Del Giovane, Cinzia; Panchaud, Alice
Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I-2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I-2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I-2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns.
Citation - WoS: 3
Citation - Scopus: 3
Obesity, Neural Tube Defects and Folic Acid- Complex Relationship
(Imr Press, 2021) Koren, Gideon; Kaplan, Yusuf C.
Obesity is associated with twofold increased risk of neural tube defects (NTD). Research has repeatedly shown that about 70% of NTD are folic-acid dependent. Yet, there is controversy whether folic acid status is the main determinant of the increased risk of obesityinduced NTD. The rational for this review is to update and discuss the evidence on the link between obesity, folic acid and NTD, in an attempt to shed light on the question whether optimal folic acid dose schedule can mitigate this risk. During pregnancy maternal folate requirements increase by 5--10-fold, as folate is diverted towards the placenta and fetus, as well as supporting different maternal organs. Correspondingly, low maternal folate status has been associated with birth defects in fetal anatomical regions particularly sensitive to reduced folate intake including oral cleft, cardiovascular defects and NTD. A recent study has documented decreased placental folate transporter expression and activity in the first and second trimesters among obese mothers. This may explain the higher incidence on NTD in infants of obese women, as less folate may find its way to the developing fetus during the sensitive periods for creating NTD. Recent pharmacokinetic results indicate that steady state levels of folate are almost perfectly defined by the dose per lean body weight (LBW). The mean dose per kg LBW that would be expected to result in steady state serum folate level of > 15.9 nmol/L was identified as 0.0073 mg/kg LBW. A large study found no differences in dietary supplementations of folic acid, yet obese women exhibited lower median serum folate as well as lower mean serum B-12 levels, but no differences in mean RBC folate levels. There was a negative correlation between increasing BMI and both serum folate and plasma B-12. Future research will be needed to incorporate more fully, in addition to evidence of NTD, obesity and folic acid intake, also direct measurements of serum and RBC folate, as well as other confounders, in order to create a model that will shed light on these complex interactions.
Citation - WoS: 21
Citation - Scopus: 23
Pregnancy Outcomes Following Maternal Exposure To Statins: a Systematic Review and Meta-Analysis
(Wiley, 2022) Karadas, Baris; Uysal, Nusret; Erol, Hilal; Acar, Selin; Koc, Meltem; Kaya-Temiz, Tijen; Koren, Gideon; Kaplan, Yusuf C.
Aims The objective of this meta-analysis was to determine whether maternal exposure to statins is associated with increased rates of major congenital malformations and other adverse pregnancy outcomes. Methods PubMed/Medline, Web of Science and Reprotox (R) databases were searched. Cohort and case control studies with prenatal exposure to statins were included. Results Analysis of five cohort studies and one case-control study showed no significant increase in rate of major congenital malformations when the exposed group was compared with the control ([OR 1.27; 95% CI 0.80-2.04], [aOR 1.05; 95% CI 0.84-1.31]). A significant increase in heart defect risk was detected in the statin-exposed group when unadjusted ORs were combined (OR 2.47; 95% CI 1.36-4.49). Further analysis of the same outcome by using adjusted ORs showed no significant increase in heart defect risk in the statin-exposed group compared with the controls (aOR 1.24; 95% CI 0.93-1.66). A significantly lower live birth rate (OR 0.60, 95% CI 0.49-0.75) and a higher spontaneous abortion rate (OR 1.36; 95% Cl 1.06-1.75) were detected in the statin-exposed group. Conclusions Gestational statin exposure was not associated with a significant increase in risk of major congenital malformations, heart defects and other adverse pregnancy outcomes, except spontaneous abortion and live birth rate, which may be associated with maternal comorbidity and other unadjusted risk factors. Further research focusing on particular statins is needed to draw more definitive conclusions.