Maternal cardiovascular profiling in the first trimester of pregnancies complicated with gestation-induced hypertension or fetal growth retardation: a pilot study

Abstract

Objective: In this study, we determine whether maternal cardiovascular (CV) profiling can detect first trimester differences between women with uncomplicated pregnancies (UP) and those who will develop gestational hypertensive disorders (GHD) or normotensive fetal growth retardation (FGR).

Methods: Cardiac, arterial, and venous function were evaluated in 242 pregnant women around 12 weeks of gestation, using impedance cardiography (ICG) and combined electrocardiogram – Doppler ultrasonography. After postnatal determination of gestational outcome, first trimester measurements were compared between groups using Mann–Whitney U test for continuous data or Fisher’s Exact test for categorical variables (SPSS 20.0).

Results: Compared to UP, first trimester aortic flow velocity index [71?±?0.96 versus 61?±?4.91 1/1000/s (p?=?0.016)], acceleration index [133?±?2.25 versus 106?±?11.26 1/100/s² (p?=?0.023)] and Heather index [23.1?±?0.35 versus 19.2?±?1.70?Ω/s² (p?=?0.019)] were lower in GHD pregnancies, and first trimester stroke volume [77?±?1.16 versus 67?±?3.97?ml (p?=?0.033)] and cardiac output [7.3?±?0.10 versus 6.2?±?0.31?l/min (p?=?0.025)] were lower in FGR pregnancies.

Conclusions: Maternal CV function in the first trimester of pregnancy differs between UP and those destined to develop GHD or FGR. This can be assessed with non-invasive maternal CV profiling, opening perspectives for the application of this technique in early gestational screening for GHD and FGR.     

Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis

Objective: To evaluate the effect of folic acid supplementation during pregnancy on the risk of gestational hypertension/preeclampsia. Methods: A systematic review and meta-analysis were conducted. Medline, Embase, Scopus, and the Web of Science were searched from inception to December 2014. Results: Out of 1224 potentially relevant studies, 13 studies met our inclusion criteria (2 randomized controlled trials (RCTs), 10 cohort studies, and 1 case–control study). The pooled relative risk (RR) and 95% confidence interval (CI) of the two RCTs were 0.62 (0.45–0.87) in the trial arm as compared with the placebo arm. The pooled RR was 0.92 (95% CI: 0.79–1.08) for nine cohort studies with available data on folic acid supplementation in pregnancy and gestational hypertension/preeclampsia. Pooled RR was 0.88 (95% CI: 0.76–1.02) for eight cohort studies with available data on folic acid supplementation and preeclampsia. Conclusion: Whether folic acid supplementation in pregnancy can prevent the occurrence of gestational hypertension/preeclampsia remains uncertain.     

Maternal and fetal outcome in women with gestational hypertension in comparison to gestational proteinuria: A 3-year observational study

Objective: To assess the maternal and fetal outcome in women with gestational hypertension in comparison to gestational proteinuria.

Methods: This was a prospective 3-year observational study carried out at Menoufia University Hospital and included 106 patients with gestational hypertension and 124 patients with gestational proteinuria after 20 weeks’ gestation. Enrolled patients were followed to assess the maternal and fetal outcome. Data were collected and tabulated.

Results: There was a highly significant difference between the two groups regarding the development of preeclampsia (PE) and persistence of the condition after the end of the puerperium (p < 0.001) with more women progressed to PE and lower number suffered persistence of the disorder in the gestational hypertension group. There was no significant difference between the two groups regarding other maternal complications (p > 0.05). There was a significant difference between the two groups regarding preterm delivery, admission to NICU, and neonatal mortality (p < 0.05) which were higher in the gestational proteinuria group. There was no significant difference between the two groups regarding other fetal and neonatal complications (p > 0.05).

Conclusions: Although gestational hypertension progressed more frequently to PE than gestational proteinuria, poorer fetal outcome was more encountered in women with gestational proteinuria. Larger studies are warranted to confirm these findings.     

Serum chemerin level during the first trimester of pregnancy and the risk of gestational diabetes mellitus

Objective: To investigate the association between chemerin level in the first trimester of pregnancy and the risk of gestational diabetes mellitus.

Methods: The blood samples of 212 women at 8–12?weeks of gestation were collected. After screening for gestational diabetes mellitus (GDM), 19 women with GDM and 20 women randomly selected from 144 women with normal glucose tolerance (NGT) were included in the study. Blood samples were collected from these women. Triglycerides, glucose, total cholesterol, and HDL cholesterol, LDL cholesterol, insulin and chemerin were measured. Gestational weight gain and body mass index was assessed.

Results: Serum levels of chemerin were significantly elevated during late gestation, and the risk of GDM was positively associated with maternal serum chemerin in the first trimester.

Conclusion: Serum chemerin level during the first trimester of pregnancy has the potential to predict risk of GDM.     

Predicting small for gestational age in the first trimester of pregnancy using maternal ophthalmic artery Doppler indices

Objective: To assess the capacity of maternal ophthalmic Doppler indices for predicting small for gestational age (SGA) newborns in the first trimester of pregnancy.

Methods: We performed a prospective observational cohort study involving 499 singleton pregnancies during the first trimester scan (11–14 weeks). The following maternal ophthalmic Doppler indices were assessed: pulsatility index (PI), first diastolic peak velocity (PD1) and peak ratio (PR)?=?PD1/peak systolic velocity. We considered SGA all newborns with weight below 10th percentile. We used chi-square test (χ²) to compare the groups. We used area under receiver operating characteristics (ROC) curves with 95% confidence intervals (CI) and detection rate of 5% of false positive of each maternal ophthalmic Doppler index and the mean uterine artery PI for prediction SGA.

Results: 27 (5.4%) patients delivered SGA newborns, 12 (2.4%) patients developed preeclampsia (PE) and delivered SGA newborns, and 460 had uneventful pregnancies (controls). We observed significant difference of PI and PR between SGA (SGA and SGA+PE) and control groups, p?=?0.043 and p?=?0.014, respectively. To 5% of false positive, the detection rate of SGA (SGA and SGA+PE groups) using PI, PD1 and PR were 14.8, 3.7, 14.8, 16.7, 16.7 and 16.7%, respectively. Mean uterine PI was significantly higher in the SGA+PE group (p?=?0.003).

Conclusion: The isolated use of maternal ophthalmic Doppler indices or in combination with uterine artery Doppler, in the first trimester of pregnancy, was not efficient to predict SGA newborns.     

Outcome of singleton preterm small for gestational age infants born to mothers with pregnancy-induced hypertension. A population-based study

Background: Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants.

Objective: To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications.

Methods: Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995–2010 (n?=?2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6?h, antepartum hemorrhage and clinical chorioamnionitis.

Results: In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50–1.16), survival without severe neurological morbidity (1.14; 0.79–1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59–1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40–1.44), survival without severe neurological morbidity (1.16; 0.64–2.12) and survival without BPD (1.04; 0.58–1.86) were also similar in the PIH versus no-PIH groups.

Conclusions: PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.     

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles

The aim of the present study was to compare the efficacy, tolerability and patients’ satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20–40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20?mg twice daily (n?=?96) or micronized progesterone 400?mg twice daily at the day of oocyte retrieval (n?=?114). The clinical success rate (31% versus 33%; p?=?0.888), miscarriage rate (5.0% versus 3.0%; p?=?0.721), ongoing pregnancy rate (30.0% versus 30.0%; p?=?1.000), implantation (22.0% versus 24.0%; p?=?0.254) and multiple pregnancy rate (5.30% versus 7.20%; p?=?0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62?±?13.83?ng/ml versus 20.66?±?18.09?ng/ml; p?=?0.001). However, there was no statistically significant difference regarding the patients’ satisfaction (p?=?0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40?mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients’ satisfaction and tolerability, for LPS among women undergoing IVF.     

Quantitative analysis of fetal DNA in maternal plasma in gestational diabetes mellitus,iron deficiency anemia and gestational hypertension pregnancies

Abstract

Objective: To quantify circulating fetal DNA (fDNA) levels in the second and third trimesters of normal healthy pregnant individuals and pregnant women with the following clinical conditions: gestational diabetes mellitus (GDM), iron deficiency anemia and gestational hypertension (GHT).

Methods: The SRY gene located on the Y chromosome was used as a unique fetal marker. The fDNA was extracted from maternal plasma and the SRY gene concentrations were measured by quantitative real-time polymerase chain reaction (PCR) amplification using TaqMan dual labeled probe system.

Results: No significant differences were observed in the mean fDNA concentration between normal and GDM pregnancy samples (p?>?0.05) and also between normal and anemic pregnancy samples (p?>?0.05) in both trimesters, but significant differences were observed between the third trimester normal and GHT pregnancy samples (p?=?0.001). GDM and iron deficiency anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma.

Conclusions: Increased amount of circulating fDNA in maternal plasma could be used for early identification of adverse pregnancies. GDM and anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma. Hence, the elevated fDNA values could be used as a potential screening marker in pregnancies complicated with GHT but not with GDM and iron deficiency anemia.     

Prediction of fetal birthweight in Taiwanese women with pre-eclampsia and gestational hypertension using an equation based on maternal characteristics

Aim:  The purpose of the present study was to develop a method for predicting the birthweight of newborns in women with pre-eclampsia and gestational hypertension based on maternal characteristics and pregnancy-related factors.
Methods:  A total of 661 consecutive pregnant women with pre-eclampsia and gestational hypertension who delivered at Chang Gung Memorial Hospital from 1994 to 2003 were included in the analysis. Multivariate regression formulas (Models I and II) were derived from maternal characteristics to predict low infant birthweight. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated and tested for these formulas.
Results:  The Model I formula was as follows:

Using a cut-off value of 2210 g, the equation predicts the occurrence of a low birthweight baby with 90.9% sensitivity. If higher specificity is required, increasing the cut-off value to 2488 g yields a specificity of 95.2%. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 93.7 (95% confidence interval [CI], 0.88 to 0.99) for low birthweight baby prediction in Model I.
Conclusion:  The results suggest that these regression formulas based on maternal characteristics may accurately predict low birthweight babies in pregnant women with pre-eclampsia and gestational hypertension. The cut-off values were determined and cross-validated by ROC curve analysis.     

Effect of epidural analgesia on maximum and minimum blood pressures during the first stage of labour in primigravidae with mild/moderate gestational hypertension

One of the arguments used in favour of epidural analgesia for hypertensive patients in labour is its effect on mean arterial blood pressure, although the fetal and maternal risk from hypertension is more closely linked to maximum recorded levels. We have therefore assessed the effect of epidural analgesia on maximum blood pressure. There was no change in the maximum systolic or diastolic blood pressure after epidural analgesia when compared to baseline values or levels in untreated hypertensive controls. We conclude that this form of analgesia should be offered to hypertensive patients purely for its analgesic effect and not as a method for blood pressure control.     

Effect of epidural analgesia on maximum and minimum blood pressures during the first stage of labour in primigravidae with mild/moderate gestational hypertension

Summary. One of the arguments used in favour of epidural analgesia for hypertensive patients in labour is its effect on mean arterial blood pressure, although the fetal and maternal risk from hypertension is more closely linked to maximum recorded levels. We have therefore assessed the effect of epidural analgesia on maximum blood pressure. There was no change in the maximum systolic or diastolic blood pressure after epidural analgesia when compared to baseline values or levels in untreated hypertensive controls. We conclude that this form of analgesia should be offered to hypertensive patients purely for its analgesic effect and not as a method for blood pressure control.     

Management of severe pregnancy-induced hypertension after 34 weeks of gestation: A prospective study to reduce the rate of cesarean section

Objective: The aim of this study was to reduce the rate of cesarean section (CS) in severe pregnancy-induced hypertension (PIH) by introducing a set of indicative criteria for CS. Methods: Labor induction was attempted in Japanese patients (n = 41) with severe PIH after 34 weeks of gestation. Vital signs and symptoms that may increase the risk of serious complications were defined. Following the appearance of one or more signs or symptoms, labor induction was suspended and CS was performed. The impact of using specific indicative criteria was evaluated by comparing the CS rate among patients who delivered before and after the criteria were introduced. Results: Labor induction was attempted in 36 of 41 patients. Among the 36 patients in whom vaginal delivery was started, 12 patients required CS, and the remaining 24 patients succeeded in vaginal delivery. The introduction of specific indicative criteria for CS was associated with a significant reduction in the CS rate, from 95% (43/45) to 41% (17/41). Conclusions: Unnecessary CS may be avoided by defining the limits of safe labor induction.     

Significance of high-normal blood pressure during early second trimester for predicting the onset of hypertensive disorders in pregnancy

Objective: The aim of this study was to determine the predictive value of high-normal blood pressure (HNBP) during the early second trimester for hypertensive disorders in pregnancy, including gestational hypertension (GH) and preeclampsia (PE). Methods: This was a retrospective single-center cohort study of 2143 singleton pregnant women. The association of HNBP, ranging from 130/85 to 139/89 mmHg between 14 and 19 weeks of gestation, with the development of hypertensive disorders was assessed by multivariable logistic regression analyses. Results: In a cohort of 2102 pregnant women, 93 (4.4%) pregnancies had HNBP during early second trimester. Pregnant women with HNBP more frequently developed hypertensive disorders than normotensive women (20.4% vs. 8.2%, p < 0.001). HNBP was significantly associated with the development of GH (adjusted odds ratio (aOR): 1.81; 95% confidence interval (CI): 1.16–3.25, p = 0.015) and PE (aOR: 6.05; 95% CI: 3.46–12.6, p = 0.013) after adjustment for confounders. Conclusion: HNBP during the early second trimester is an independent risk factor for both GH and PE.     

Ibuprofen use to reduce the incidence and severity of bronchopulmonary dysplasia: a pilot study.

OBJECTIVE: To assess the safety and efficacy of ibuprofen in reducing the incidence and severity of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: A total of 18 premature infants between 23 and 28 weeks' gestation were studied. Ibuprofen (10 mg/kg of loading dose followed by 5 mg/kg every 12 hours) was administered intravenously or orally to nine infants on respiratory support at > or = 7 days of age and was continued until 28 days of life or until the infants were spontaneously breathing room air, whichever occurred earlier. Ibuprofen levels in plasma were measured in five of these infants. The outcome variables (BPD, ventilatory parameters, and complications) in the study group were compared with those in nine matched controls treated conventionally. RESULTS: The incidence of BPD at 36 weeks postconceptional age was similar in both groups (eight of nine in each group). The percentage of oxygen requirement, the ventilatory efficiency index, and steroid use were also similar in both groups. One infant in the study group, who was also receiving steroids and aminophylline, developed gastrointestinal hemorrhage. Reversible renal failure in one infant and necrotizing enterocolitis in another infant were seen at 4 and 21 days, respectively, after the last dose of ibuprofen. There was no difference in the incidence of intraventricular hemorrhage between the two groups. Plasma levels of ibuprofen at 3 hours after the first dose ranged from 10.3 to 36 mg/liter. Study infants tolerated the feeds better and achieved the full enteral goal earlier than controls (p = 0.04). CONCLUSION: Although a trend toward less ventilator and hospital days in the ibuprofen group was observed in this pilot study, the differences were not statistically significant. The incidence of BPD was similar in both groups. In the study group, two infants developed gastrointestinal complications and a third infant experienced reversible renal failure. The plasma ibuprofen levels were low. Further studies are needed to assess the use of ibuprofen for the prevention and/or treatment of BPD in preterm infants.     

Comparison of first trimester transvaginal anatomy scan to the second trimester structural survey in normal weight and obese populations: a pilot study

Purpose: To compare visualization of first trimester fetal anatomic transvaginal ultrasound (TVUS) to the second trimester transabdominal anatomic ultrasound (TAU) in normal weight and obese patients.

Materials and methods: In a prospective cross-sectional study design, 25 women underwent a TVUS between 12 and 14 weeks, and a TAU at 18–22 weeks. For each anatomic structure, the percentage of patients achieving optimal visualization was recorded. Risk ratios for visualizing a structure in the second trimester versus the first were calculated.

Results: Twenty-five patients underwent a TVUS and 24 completed the TAU. The average BMI in the obese and nonobese groups was 34?kg/m² and 23?kg/m², respectively. All structures were more consistently visualized during the TAU for the both groups. The cardiac views, hands and feet were more difficult to visualize in all the patients at both scan times but were more frequently visualized in the TAU. For the obese patients, hands, feet, cardiac and spine views were less frequently visualized in both the scans. The posterior fossa and profile views were more difficult to obtain in the TVUS.

Conclusions: The first trimester TVUS detects many of the structures assessed during an anatomic survey; however, it is not superior to the second trimester TAU in normal weight and obese patients.     

Determination of the fetal myocardial performance index in women with gestational impaired glucose tolerance and to assess whether this parameter is a possible prognostic indicator of adverse fetal outcome

Aim: The aim of this study was to investigate if the myocardial performance index (MPI) is altered in fetuses in women with gestational impaired glucose tolerance (GIGT), controlled on diet and whether this parameter is also predictive of adverse outcome in this group, as in poorly controlled gestational diabetes.

Methods: In a prospective cross-sectional study, 32 women with GIGT on diet in the 3rd trimester were recruited and matched with 32 women with normal pregnancies (control group). Using Doppler echocardiography, the MPI was calculated. Placental resistance Doppler markers in both groups were also determined. An abnormal outcome was defined as any of the following: stillbirth, neonatal death, neonatal intensive care unit (NICU) admissions, tachypnea with pulmonary oedema, neonatal cord pH <7.15, five minute Apgar score <7, and cardiomyopathy.

Results: The cases had a significantly higher median MPI compared to controls, p value <.0001. There were eight abnormal outcomes recorded in the 32 fetuses in the study group, corresponding to an adverse outcome rate of 25%. Fetuses with an adverse outcome had significantly higher MPI measurements compared to the GIGT fetuses with normal outcome. The MPI served as an excellent predictor of adverse outcome in the GIGT fetuses, with a total area under the ROC curve of 0.96. An MPI z-score greater than 4.0 conferred a sensitivity of 100% and specificity of 80%. No abnormal outcomes were noted in the control group.

Conclusions: The MPI is impaired in fetuses in GIGT women, with fetuses with an adverse outcome having significantly higher MPI measurements compared to the fetuses with normal outcome in the GIGT group. MPI has the potential to improve fetal surveillance in gestational diabetes.