Association between fragile X premutation and premature ovarian failure: a case–control study and meta-analysis

Aim

The aim of the present study was to investigate the association between FMR1 premutation and premature ovarian failure (POF) patients in Indian population, and a meta-analysis of published results was undertaken to clarify whether FMR1 premutation consistently contributed to the susceptibility.

Methods

A total of 289 POF samples and 360 control samples were included in the study. Repeat variation was checked using GeneScan technique. Results were analyzed with GeneMapper software. Meta-analysis was performed using the Open Meta-Analyst and STATA 12.0 software. The crude odds ratio with 95 % confidence interval (CI) was computed to assess the strength of the associations.

Results

The assayed case and control population showed 29 different CGG repeat sizes (alleles), ranging from 7 to 40. Within this population, we found that the CGG repeat length polymorphisms were within the normal range of 6–55 in both patients as well as control samples. Eleven case–control studies were included in the meta-analysis with a total of 1,313 POF cases and 3,132 control subjects. Our meta-analysis revealed that there was a significant difference in the incidence of FMR1 premutation between POF cases and control subjects with p value <0.001 (OR 5.41; 95 % CI 2.53, 11.61).

Conclusions

We found no significant association between FMR1 CGG repeat premutation and POF in Indian population. However, the meta-analysis showed an increased risk of POF associated with a premutation, especially among populations from European descent. Further functional research should be performed to explain the inconsistent results in different ethnicities and POF susceptibility.     

The relationship of fat soluble antioxidants with gestational diabetes in Iran: a case–control study

Abstract

Objective: The primary aim of this study was to evaluate the relationship of fat soluble antioxidants (retinol and α-tocopherol) with gestational diabetes (GDM).

Methods: This was a case–control study in which 41 pregnant women with GDM and 41 healthy women were recruited. The inclusion criteria were gestational age ≥32 weeks, singleton foetus, nulliparous or parous women up to four pregnancies and normal fasting blood sugar in the early pregnancy. Two groups were matched regarding age, gestational age and body mass index. A 5?ml venous blood sample were drawn and analysed with the chromatograph for measuring retinol and α-tocopherol. Data were analysed through Chi-square and t test.

Results: The mean serum retinol of the GDM group was 0.46?µg/dl and in the control group it was 0.59?mg/dl (p?=?0.01).The mean α-tocopherol in the women with GDM was 6.21?mg/dl and in the control group it was 6.92?mg/dl (p?>?0.05).

Conclusion: The level of retinol in the diabetic pregnant women was significantly lower than that in the control group. This reduction may be due to the reduced antioxidant defences in women with GDM.     

Association of maternal serum homocysteine concentration levels in late stage of pregnancy with preterm births: a nested case–control study

Purpose: To investigate the relationship between maternal serum homocysteine (Hcy) levels in the late stage of pregnancy and preterm birth. Other relevant biochemical parameters were measured to establish the normal reference interval of serum Hcy in both women in the late stage of pregnancy and neonates.

Materials and methods: The nested case–control study included 300 singleton pregnant women with preterm births between June 2013 and May 2015 and their premature delivered babies as a preterm group. Blood sample within three days before delivery was collected. Simultaneously, 300 healthy pregnant women admitted during the same time, and singleton mature neonates who had gestational week-matched blood sample were age-matched as a control group.

Results: Maternal serum levels of Hcy, total triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), free fatty acids (FAA) and superoxide dismutase (SOD) were all higher in the preterm group than in the control group except high-density lipoprotein cholesterol (HDL-C). Serum levels of Hcy, TC, LDL-C, UA, FAA and SOD were higher in prematurely delivered neonates than in the control group except for HDL-C. The body weight of prematurely delivered neonates was negatively correlated with the maternal serum levels of Hcy and UA before delivery.

Conclusions: Higher maternal serum Hcy levels were associated with preterm birth and neonatal body weight. Elevated maternal serum levels of Hcy might serve as a biomarker for preterm birth prediction.     

Can first trimester maternal serum follistatin like 3 levels predict developing gestational diabetes mellitus?

Purpose: The purpose of this study is to determine whether the first trimester maternal serum levels of follistatin like 3 (FSTL3) are altered in patients who develop gestational diabetes mellitus (GDM).

Methods: This is a prospective nested case-control study that included 170 singleton pregnant women recruited in their first trimester. All women were followed up until the delivery and 144 of them completed the study. The maternal serum levels of FSTL3 were measured at 11–14 weeks of gestation. The GDM-affected women (n?=?19) were compared with the GDM-free control women (n?=?125) for potential serum biomarkers including the FSTL3 levels.

Results: There were no significant differences in maternal age, maternal pre-pregnancy body mass index, and neonatal birth weight between the GDM group and the GDM-free control group. Women with GDM had significantly greater weight gain during pregnancy than the women without GDM. Serum concentration of glycosylated hemoglobin was significantly higher in women with GDM. There were no significant differences in serum FSTL3 levels (p?=?0.578) between the GDM group and the GDM-free control group.

Conclusions: Our results suggest that the first trimester maternal serum FSTL3 levels are not altered in women who develop GDM and thus do not support the use of serum FSTL3 levels for early prediction of GDM.     

Anti muellerian hormone serum levels in women with endometriosis: A case–control study

Objective.?To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis.

Design.?A case–control study

Setting.?Women's General Hospital, Linz, Austria.

Patient(s).?Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group).

Interventions.?None.

Main outcome measures.?AMH serum level.

Results.?Mean AMH serum level was significantly lower in the study than in the control group (2.75?±?2.0?ng/ml vs. 3.46?±?2.30?ng/ml, p?<?0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28?±?1.93?ng/ml vs. 3.44?±?2.06?ng/ml; p?=?0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38?±?1.83?ng/ml vs. 3.58?±?2.46?ng/ml; p?<?0.0001).

Conclusion.?Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.     

No association between periodontitis and preterm low birth weight: a case–control study

Purpose

This study aimed to investigate the association between periodontitis in pregnant women and adverse pregnancy outcomes by heeding confounding risk factors for preterm low birth weight infants.

Methods

This study was reported according to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. A case–control study was conducted. Medical records of all pregnant women attending a prenatal care clinic were screened. Those between 21 and 34 years and gestational age of 28–32 weeks were initially enrolled in the study. The exclusion criteria were then applied: diabetes mellitus, genitourinary tract infections, or HIV infection; previous multiple gestations; previous preterm birth/low birth weight infants; in vitro fertilization procedures; placental, cervical/uterine abnormalities; history of infertility; history of drug abuse; and any medical conditions that required antibiotics prophylaxis. Patients’ anthropometric, demographic, and behavioral characteristics were collected. The periodontal clinical parameters were obtained from six sites per tooth: clinical attachment level, probing pocket depth, dental plaque index, and gingival bleeding index. Women were then allocated into two groups: mothers of preterm and/or low birth weight newborns (cases) and mothers of full-term and normal birth weight newborns (controls).

Results

Periodontal clinical parameters were analyzed and reported separately for each group, and no significant differences were observed (p > 0.05). Logistic regression analysis revealed that periodontal clinical parameters were not associated with the adverse pregnancy outcomes.

Conclusion(s)

After controlling for confounding factors, our results suggest that maternal periodontal disease is not a risk factor associated with preterm low birth weight infants.

     

Preeclampsia and depression: a case–control study in Tehran

Purpose

This study was conducted to determine the correlation between preeclampsia and depression.

Methods

Participants in this study included 156 cases with preeclampsia and 156 controls without any history of preeclampsia who were all newly admitted to antepartum wards, emergency room wards, and labor and delivery wards of the study hospitals (Valieasr, Shariatti, Mirza Koochak Khan, Shahid Akbar Abadi, Baharloo and Arash). They consented and completed a questionnaire on demographic characteristics, obstetric, delivery and infant information and Patient Health Questionnaire (PHQ-9) to assess their depression status. Data were analyzed through independent t test, Mann–Whitney U test, Chi-squared test, Fisher’s exact test and multiple regression by SPSS and STATA.

Results

Moderate to severe depression was found in 31.2% of the cases and 24.8% of the controls. Women with no depression in comparison with women with mild depression had a 1.81-fold (95% CI 1.05–3.14; P = 0.03) increased risk of preeclampsia, while moderate to severe depression correlated with a 2.52-fold increase (95% CI 1.05–6.02; P = 0.03) after adjustment of the probable confounding variables.

Discussion

With regard to the high prevalence of moderate to severe depression and its association with preeclampsia, our findings support and suggest efforts for screening depression among pregnant women and appropriate educational studies for mental and psychological problems during pregnancy.     

Is vaginal progesterone treatment associated with the development of gestational diabetes? A retrospective case–control study

Purpose

To determine the incidence of gestational diabetes mellitus (GDM) in pregnant women who received vaginal progesterone due to short cervical length or to prevent recurrent preterm birth.

Methods

In this retrospective study, we included 190 women with singleton pregnancies at risk for preterm birth who received vaginal natural progesterone (200 mg daily between gestational weeks 16?+?0 and 36?+?0) for a minimum of 4 weeks and delivered?>?28 weeks. The control group consisted of 242 age- and body mass index (BMI)-matched patients without progesterone administration. Data were acquired from a database containing prospectively collected information. Patients with pre-existing diabetes, and conception after in vitro fertilisation procedure were excluded.

Results

The incidence of GDM did not differ significantly between the progesterone-treated and the control group (14.7% vs. 16.9%, respectively; p?=?0.597). In a binary regression model, patients with higher pre-pregnancy BMI (OR 1.1; p?=?0.006), and those with a family history of diabetes had a higher risk for GDM development (OR 1.8; p?=?0.040), whereas vaginal progesterone treatment had no significant influence (p?=?0.580).

Conclusion

The use of vaginal progesterone for the prevention of recurrent preterm delivery and in women with a short cervix does not seem to be associated with an increased risk of GDM.

     

The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case–control study

Purpose

To study the effects of gestational transient thyrotoxicosis (GTT) on pregnancy outcomes.

Methods

This case–control study retrospectively analyzed 7976 women with singleton pregnancies whose thyroid function was measured before 16 weeks of gestation and who delivered at ≥22 weeks of pregnancy. GTT was defined as hyperthyroidism (free thyroxine [FT4] level: ≥95th percentile) in the early pregnancy, which normalized in mid-pregnancy without thyroid-stimulating hormone receptor antibodies. Using data extracted from electronic records, we examined the association between GTT and the pregnancy outcomes (preterm delivery, gestational age at delivery, pregnancy induced hypertension (PIH), preeclampsia, placental abruption, caesarian section, birth weight, low birth weight, Apgar score, cord pH, stillbirth at gestational week ≥22, and neonatal death). We classified the cases into quartiles according to their FT4 values during the early pregnancy and investigated the association with the gestational age at delivery.

Results

Two hundred and eight cases of GTT and 6317 cases with normal thyroid assessments were reviewed. GTT was associated with hyperemesis gravidarum, but not with stillbirth, preterm delivery, PIH, preeclampsia, placental abruption, or low birth weight. The gestation period was shorter in patients with GTT than in those with a normal thyroid function (38.69 ± 1.79 vs. 39.07 ± 1.64 weeks, p < 0.01). Higher FT4 levels during the early pregnancy were associated with earlier delivery (p = 0.02).

Conclusions

GTT was associated with a lower gestational age at delivery but not with adverse pregnancy outcomes. There was a negative correlation between the FT4 values in the early pregnancy and the gestational period.

     

Screening of gestational diabetes mellitus: a new consensus?

The choice of thresholds to diagnose gestational diabetes mellitus (GDM) is a topic of ongoing controversy. In 2008, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study showed continuous graded relationships between increasing maternal plasma glucose and increasing frequency of adverse perinatal outcomes. Macrosomia (birth weight>90th percentile for gestational age), primary cesarean delivery, clinical neonatal hypoglycemia and hyperinsulinemia (cord serum C peptide>90th percentile) were all related to each of the 3 glucose values (fasting plasma glucose and at 1 and 2 hours after the 75 g oral glucose test). The associations were continuous with no obvious thresholds at which risks increased. The International Association of Diabetes and Pregnancy Study Group (IADPSG) recently issued recommendations that the diagnosis of GDM be made when any of the following thresholds are met or exceeded: fasting plasma glucose: 0,92 g/L; 1 hour: 1,80 g/L; or 2 hours: 1,53 g/L after the 75 g oral glucose test. These criteria were chosen to identify pregnancy with increased risk of adverse perinatal outcomes. By the new criteria, the total incidence of gestational diabetes in the HAPO population was 17, 8%. Fasting plasma glucose (FPG) in early pregnancy appears as an important predictive factor. Higher first trimester FPG (lower than those diagnostic of diabetes) are associated with increased risks of later diagnosis of gestational diabetes and adverse pregnancy outcomes. Whether this new consensus will be adopted by public health bodies and professionals remains to be seen.     

Placental expression of endothelial and inducible nitric oxide synthase and NO metabolism in gestational hypertension: a case–control study

Objective: Hypertension is one of the most common medical disorders in pregnancy and a role of nitric oxide (NO) metabolism has been described. Thus, the present work aimed at determining placental gene expression of eNOS and iNOS, to measure NO and ONOO^? levels in patients with gestational hypertension (GH).

Methods: Fifteen patients with GH and 15 healthy pregnant controls were enrolled in the study. Placental tissue was taken immediately after delivery and was stored at ?80?°C until analysis. A piece of frozen tissue was homogenized in the appropriate buffer. Total RNA was extracted and was reverse transcribed to obtain complementary DNA that was used for real-time PCR for iNOS and eNOS expression, whereas NO and ONOO^? production were measured by commercially available kits.

Results: Placental eNOS and iNOS mRNA levels were significantly reduced in GH when compared to controls. NO and ONOO^? production were both significantly higher in GH than controls.

Conclusions: The reduced eNOS and iNOS gene expression in women with GH reinforces the hypothesis that the mechanisms involving NO pathways, may promote oxidative damage, by contributing to the reduced blood flow and increased resistance in the feto–maternal circulation and suggests the use of NO modulators as useful tools in GH management.     

Could serum levels of irisin be used in gestational diabetes predicting?

ObjectiveGestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy leading to acute and chronic complications in both mother and newborn. The pathogenesis of GDM has not been fully understood, However, since the disease shares risk factors with type 2 diabetes mellitus (T2DM), a relationship between these two disease states is plausible. The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate the relationship between irisin levels and gestational diabetes mellitus and the possible benefits of the metabolic profile.Materials and methodsWe performed a cross-sectional analysis of circulating levels of irisin in 100 pregnant women similar for age and body mass index and the groups included 50 gestational diabetic patients and 50 healthy pregnant volunteers. Serum irisin levels were measured by ELISA kit.ResultsMean age and body mass index levels were similar in both groups. Median HbA1c, fasting blood glucose, Glucose 1 h, Glucose 2 h and fasting insülin levels were higher in with gestational diabetic patients compared to the control group. In gestational diabetic group, the median irisin level was lower than in the control group.ConclusionSerum irisin levels were lower in gestational diabetic patients. Further investigations are needed to explore the underlying biological effects of irisin on pregnant women.     

Positive airway pressure levels and pneumothorax: a case–control study in very low birth weight infants

Objectives.?Evaluate the incidence of pneumothorax (PTx) and the levels of positive airway pressure (Paw) applied to very low birth weight infants during the first 5 days of life (DOL), after evidence-based protocols using early continuous positive airway pressure (CPAP) and high levels of Paw (CPAP or mean airway pressure) were implemented.

Methods.?From 2004 to 2007, all infants submitted to assisted ventilation that developed PTx were identified. Controls were matched by birth weight, gestational age, and type of ventilatory support. Paw levels were averaged on a time-weighted basis. A p value?<0.05 was considered significant.

Results.?A total of 25 infants developed PTx (3.8%); 23 during the first 5 DOL. PTx was diagnosed at 14?h of life (1.3–80?h) when 74% were treated with mechanical ventilation. In controls, Paw decreased over time whereas in PTx infants it did not decline until after 80?h. PTx infants had an increase in Paw from 12?h up to 6?h prior to the diagnosis.

Conclusion.?The rate of PTx was low even after the implementation of the protocols. An association between Paw levels and PTx was observed but until the precise time of onset of a PTx can be determined this should be regarded either as an early signal or as an indicator of more severe lung disease.     

Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11–14 weeks of gestation

Objective: To evaluate whether gestational diabetes mellitus (GDM) requiring insulin treatment (White’s classification A2) is associated with an alteration of pregnancy-associated plasma protein-A (PAPP-A) serum levels at first-trimester screening between 11 and 14 weeks of gestation. Methods: We collected data (2007–2010) of all women who developed GDM requiring insulin treatment and completed first-trimester combined screening program including the determination of serum PAPP-A and free β-human chorionic gonadotropin (β-hCG). A total of 288 women were included in this study. Each of the 72 women who developed GDM was matched with three unaffected controls. Results: Women with GDM were significantly older (34.2 ± 5.9 vs. 32.3 ± 5.5 years, P = 0.007) and delivered significantly earlier (38.40 ± 2.25 vs. 39.1 ± 2.2 gestational weeks, P = 0.01). Multiple regression analysis revealed, that PAPP-A and β-hCG were independently associated with each other (P = 0.04) but there was no association between GDM/no GDM and the first-trimester serum markers (P = 0.77). Conclusion: Our data suggest that women who are developing GDM needing insulin treatment do not have altered PAPP-A levels at 11–14 weeks.     

Is there a standard biological screening of gestational diabetes mellitus?

Universal screening for gestational diabetes mellitus (GDM) is contentious. There is insufficient evidence that universal screening for GDM substantially reduces perinatal complications such as cesarean section and Erb's palsy.However, risk assessment for GDM should be undertaken at the first prenatal visit and selective screening should be performed in high-risk women: diabetes mellitus in first-degree relatives, member of an ethnic group with a high prevalence of diabetes mellitus, body mass index > or 25 kg/m2, personal history of hyperglycemia or GDM, previous poor obstetric outcome. During the first trimester, a fasting glycemia over 1.05 g/l is associated with perinatal complications and should be treated. If fasting glycemia is below this level or unknown, or if glucosuria occurs, they should be re-tested between 24 and 28 weeks of gestation using a 75-g oral glucose load. The actual proposed glucose threshold values for GDM are, respectively, 1.05 and 1.55-1.60 g/l for fasting and 2 h.     

Risk factors for preeclampsia: a case–control study

Objective: To explore the risk factors of preeclampsia and provide information for prevention of preeclampsia among obstetrical patients. Methods: A case–control study was designed to find the risk factors of preeclampsia among obstetrical patients by logistic regression analysis. Results: The risk factors for pregnant women were older gestational age, increasing body mass index, living in the countryside or small towns, fewer antenatal visits, and cold seasons. Conclusions: Health education should be emphasized to encourage women to have children at a relatively younger age and control weight during pregnancy. Special measures should be taken to improve the living condition and prenatal care in the countryside and small towns.     

Relation between first trimester maternal serum leptin levels and body mass index in normotensive and pre-eclamptic pregnancies – Role of leptin as a marker of pre-eclampsia: A prospective case–control study

Objective.?We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels.

Methods.?Bloods samples were collected at 13 weeks. Non-parametric tests, Spearman's correlation, linear regression analysis and multiple logistic regression analysis were applied in our data.

Results.?1?kg/m² increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242–2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873–2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (≥25.3?ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8–194, p?=?0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018–1.133, p?=?0.009).

Conclusion.?Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case–control studies is required to clarify the predictive value of pre-eclampsia.     

Metformin – a potentially effective drug for gestational diabetes mellitus: a systematic review and meta-analysis

Metformin has been gradually used in the management of gestational diabetes mellitus (GDM). In order to prove the safety and efficacy of metformin used in pregnancy, we searched several databases for the reports of randomized trials comparing insulin and metformin used in GDM and conducted a meta-analysis. Data showed the rates of neonatal large for gestational age, cesarean section, neonatal respiratory distress and preterm birth were similar in both groups. Maternal glycated hemoglobin-% at gestational week 36–37 was significantly lower in metformin group, indicating good glycemic control of metformin. Maternal weight gain since enrollment to gestational week 36–37 was also lower in metformin group, making metformin worth using even when metformin is insufficient and supplementary insulin is needed. Data also showed that metformin significantly reduced the gestational hypertension complications in GDM patients, probably by reducing the endothelial activation and maternal inflammatory response of insulin resistance. Although metformin can cross the placenta, it is less likely to cause severe neonatal hypoglycemia compared with insulin since it neither stimulates pancreatic insulin release nor increases circulating insulin levels. According to most maternal and neonatal outcomes, metformin is an effective and safe alternative to insulin for GDM patients.     

Obstetric and neonatal outcomes in a home-like birth centre: a case–control study

Purpose

To compare the intervention rates associated with labor in low-risk women who began their labor in the “home-like birth centre” (HLBC) and the traditional labor ward (TLW).

Methods

This retrospective study used data that were collected from January 2005 to June 2008, from women admitted to the HLBC (n = 316) and compared to a group of randomly selected low-risk women admitted to the TLW (n = 890) using the Baysian information criterion to select the best predictive model.

Results

Women in the HLBC had spontaneous vaginal deliveries more often (88.6 vs. 82.8 %, p value 0.034) and perineal lesions less often (60.1 vs. 62.5 %, p value 0.013). The frequency of adverse neonatal outcomes did not differ statistically between the two groups, although the mean clamped at birth umbilical arterial pH level was higher in the HLBC group. The transfer rate from HLBC to TLW was 31.3 % of which 75.8 % were nulliparae.

Conclusions

It appears that women could benefit from HLBC care in settings such as the one studied. Larger observational studies are warranted to validate these results.