Volume 43, Issue 3

Objective: To identify the accuracy of diagnosing postpartum diabetes and glucose intolerance using antepartum glycosylated hemoglobin (HbA 1c ) and fasting glucose values. Study Design: A retrospective Hawaiian cohort of women with gestational diabetes during 2004–2011 were evaluated. Antepartum HbA 1c and postpartum 75-g glucose tolerance tests were obtained. Results: An antepartum HbA 1c value of ≥6.5% had a 45.7% sensitivity, a 96% specificity and a 40% positive predictive value (PPV) for predicting postpartum diabetes. An antepartum HbA 1c value of ≥6.5% had a 6.6% sensitivity, a 94.2% specificity and a 27% PPV for predicting postpartum impaired glucose tolerance. An antepartum HbA 1c value of ≥6.5% had a 10.3% sensitivity, a 95.7% specificity and a 33.3% PPV for predicting postpartum impaired fasting glucoses. Conclusion: We could not demonstrate a clinically useful PPV for diagnosing postpartum diabetes or glucose intolerance using an antepartum elevated HbA 1c value of ≥6.5% or a fasting glucose level of ≥90 mg/dL.

Objective: To predict gestational diabetes mellitus (GDM) or normoglycemic status using first trimester maternal characteristics. Methods: We used data from a prospective cohort study. First trimester maternal characteristics were compared between women with and without GDM. Association of these variables with sugar values at glucose challenge test (GCT) and subsequent GDM was tested to identify key parameters. A predictive algorithm for GDM was developed and receiver operating characteristics (ROC) statistics was used to derive the optimal risk score. We defined normoglycemic state, when GCT and all four sugar values at oral glucose tolerance test, whenever obtained, were normal. Using same statistical approach, we developed an algorithm to predict the normoglycemic state. Results: Maternal age, race, prior GDM, first trimester BMI, and systolic blood pressure (SBP) were all significantly associated with GDM. Age, BMI, and SBP were also associated with GCT values. The logistic regression analysis constructed equation and the calculated risk score yielded sensitivity, specificity, positive predictive value, and negative predictive value of 85%, 62%, 13.8%, and 98.3% for a cut-off value of 0.042, respectively (ROC-AUC – area under the curve 0.819, CI – confidence interval 0.769–0.868). The model constructed for normoglycemia prediction demonstrated lower performance (ROC-AUC 0.707, CI 0.668–0.746). Conclusions: GDM prediction can be achieved during the first trimester encounter by integration of maternal characteristics and basic measurements while normoglycemic status prediction is less effective.

Objective: Pre- or early-pregnancy obesity carries significant health implications. This retrospective cohort study investigates the association between pre- or early-pregnancy body mass index (BMI) and the risk of fetal and neonatal death in pregnancies implicated by obesity in a Mediterranean country. Study design: Data on pregnancies delivered during 2003–2008 at a University hospital was linked to data from regional registry. Logistic regression models were used to determine the odds ratios of a spontaneous fetal death and perinatal death among overweight, obese, and morbid obese women. Results: Independent predictors of fetal death were maternal prepregnancy BMI over 25, maternal age, maternal co-morbidities, and maternal residence in an island. Perinatal mortality was independently correlated to neonatal birthweight, maternal age, maternal residence in towns and villages, and maternal BMI over 40. Overall, maternal residence in an island, maternal autoimmune disease, and maternal prepregnancy BMI (over 25) were independent risk factors predicting offspring death (both intrauterine and perinatal). Conclusions: Maternal obesity is correlated to offspring’s mortality during fetal and/or perinatal period. This is one of the very few studies in a Mediterranean country. This study underlines the need for public health interventions to prevent obesity in young women.

Aim: To investigate first trimester maternal characteristics of women with impaired glucose tolerance that deliver large for gestational age (LGA) infants. Methods: Nested analysis from a prospective study of singleton pregnancies enrolled at first trimester. We studied women with an abnormal 1 h glucose challenge test that had normal follow-up oral glucose tolerance testing. Maternal characteristics, ultrasound parameters and serum analytes were stratified by subsequent delivery of an LGA infant. Parameters identified as significant on univariate analysis were used for a derivation of prediction by logistic regression. Odds ratio and prediction performance was determined using receiver operator curve (ROC) statistics. Results: A total of 33/114 (28.9%) women meeting the criteria delivered LGA infants. Maternal height (cm), and first trimester pregnancy-associated protein-A and free β-hCG (MoM) predicted delivery of an LGA infant (ROC area under curve 0.73; 95% CI 0.63–0.83). At a cutoff value of 0.172 the prediction rule achieved 91% sensitivity, 44% specificity, 41% positive predictive and 92% negative predictive value. Conclusion: Maternal height and first trimester high free β-hCG and PAPP-A levels may be used as predictors for delivery of LGA infants in women with impaired glucose tolerance.

Objective: To determine levels of galectins (gal)-1 and -3 (implicated in angiogenesis/immunologic mechanisms) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies, as these groups differ in fat mass, angiogenic patterns and immune responses. Methods: Cord-blood (UC) gal-1 and -3 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA singleton full-term infants and their mothers (MS). Results: IUGR, LGA and AGA groups did not differ in gal-1 and -3 concentrations. UC gal-1 levels were lower when mothers were older [b=–0.651, CI 95% –1.186 (–0.116), P=0.018] and UC gal-3 levels were increased when mothers presented gestational diabetes [b=9.836, CI 95% 3.833- (15.839), P=0.002]. In IUGRs MS gal-3 and in LGAs UC gal-1 were decreased in multiparas [b=–5.372, CI 95% -9.584- (–1.161), P=0.014], and [b=–7.540, CI 95% -14.606- (–0.473), P=0.037], respectively. No correlations were found between MS or UC gal-1 and gal-3 concentrations. Conclusions: Lower UC gal-1 levels, when mothers were older, and increased UC gal-3 levels in cases of gestational diabetes, possibly reflect angiogenic activity. In multiparas, decreased MS gal-3 and UC gal-1 levels in IUGR/LGA, respectively, might imply inflammatory response against immunosuppression expected in subsequent pregnancies, as compared to the first one.

There is a strong epidemiological association between maternal obesity and gestational diabetes mellitus (GDM). Since the publication of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study on women with mild hyperglycemia in 2008, new criteria have been introduced in maternity services internationally for the diagnosis of GDM. As a result, the diagnosis of GDM may be made in one-third of obese women (n=68). The aim of this review was to examine the interplay between maternal obesity and GDM in light of the HAPO study and the subsequent revised diagnostic criteria. Obesity and GDM are important obstetric risk factors because they both are potentially modifiable. However, the new international criteria for the diagnosis of GDM have serious resource implications for maternity services provided to the large number of women attending for care in developed countries. Further consideration needs to be given as to whether obese women with mild hyperglycemia need to be referred to a multidisciplinary team antenatally if they do not require insulin treatment.

Aims: In the Islamic religion, Ramadan is a month in the year that is passed by fasting. Healthy adult individuals are prohibited to eat, drink, and smoke from sunrise to sunset. In the present study, our aim was to assess the relation of Ramadan fasting with fetal development and maternal-fetal Doppler indices in pregnant women. Methods: This is a prospective case-control study carried out in the month of Ramadan in 2013 (9 July–7 August). One hundred and six pregnant women at the second and third trimesters of pregnancy were enrolled into the study. The sample size of the fasting group was 83 and the non-fasting group sample size was also 83. Fetal biometric measurements, such as biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal weight, amniotic fluid index, and Doppler indices of both uterine and umbilical arteries were evaluated by gray scala and color Doppler ultrasound at the beginning and end of Ramadan. Results: At the end of the Ramadan, increase in biparietal diameter, head circumference, and femur length showed a statistically significant difference from initial measurements (P<0.05). When fasting and non-fasting groups were compared separately, an increase in amniotic fluid index was statistically significant in the non-fasting group (P<0.05). Conclusion: We demonstrated some adverse effects of Ramadan fasting on fetal development. In the Islamic religion, pregnant individuals have the privilege of not fasting; therefore, they should consider postponing fasting to the postpartum period, especially in the summer season. If they are willing to do so, an appropriate nutritional program should be recommended.

Objective: Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Methods: Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Results: Antepartum maternal omentin levels were negatively correlated with insulin levels (r=–0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=–0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2–76.2 ng/mL vs. 53.4, 39.8–69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3–74.2 ng/mL, P=0.77) and did not correlate (P=0.6). Conclusions: Circulating maternal omentin levels are correlated with insulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Objective: To determine the reproducibility of the oral glucose tolerance test (OGTT). Design: A retrospective study of 205 women who underwent screening for gestational diabetes. Setting: A university teaching hospital in a South African city. Sample: Women who had an abnormal OGTT had the test repeated during the same pregnancy without any diabetic or dietary advice given in the intervening time period. Methods: Women with two OGTTs in the same pregnancy had a proforma completed at the time. Completed proformas were filed and reviewed for the purpose of this study. Main outcome measure: The κ statistic was used for estimating the agreement between repeated tests using the same nominal or dichotomous scale. Results: The OGTT was repeated during the index pregnancy in 205 women and in a subset of 76 women within 17 days. The κ statistic was 0.269 for 205 women and 0.212 for 76 women for the fasting glucose value (fair strength of agreement). The κ statistic for the 2-h glucose value was 0.157 for 205 patients and 0.174 for 76 patients (slight strength of agreement). The overall OGGT classification produced κ statistics of 0.167 and 0.150 for the whole group and the 76 patients, respectively. Conclusion: The reproducibility was better with the fasting glucose and less with the 2-h result and the overall OGGT classification. Caution needs to be exercised when interpreting the single positive result of an OGTT in pregnant women.

Aim: To assess factors contributing to cord venous glucose homeostasis in term infants delivered by elective cesarean section. Methods: Observational study of women-infant pairs at delivery. Biochemical and clinical data were collected about factors which might affect the levels of glucose, lactate, norepinephrine, epinephrine, cortisol, human growth hormone, glucagon, and insulin. Results: In the context of this data-set, three models explained a substantial amount regarding the variation: 79% of the variation in cord glucose levels is explained by levels of maternal glucose, cord venous pH, and cord lactate; 77% of the variation of cord lactate is explained by levels of cord venous pH, valine, maternal lactate and glucose, and cord norepinephrine; and 71% of the variation in cord norepinephrine is explained by levels of cord venous pO 2 , maternal lactate, cord insulin, cord GABA (gamma-aminobutyric acid), cord lactate, cord epinephrine, cord norepinephrine sulfate, and cord valine. Conclusions : Term infants delivered by cesarean section are relatively hyperinsulinemic (insulin:glucose ratio of 2.4) and glucose levels are strongly associated with maternal glucose levels, cord pO 2 , and lactate levels. There were no associations with levels of cord glucose and levels of cortisol, epinephrine and lactate, which have been shown to be important contributors to postnatal glucose homeostasis in some infant groups.

Objectives: The purpose of this retrospective controlled study is to estimate the risk for fetal loss and preterm delivery attributed to second trimester amniocentesis from a single tertiary center. Methods: The study group consists of 12,413 singleton pregnancies with consecutive amniocenteses, performed in a single tertiary center during a 15-year period (1996–2010) with known pregnancy outcome. The control group consisted of 6993 pregnancies with negative second trimester screening for aneuploidies during the same period who did not have any invasive test. The two groups were compared in terms of fetal loss rate up to 24 weeks and premature deliveries. Results: Total fetal loss up to 24 weeks in the study group, excluding terminations of pregnancy, was estimated at 1.25% (1.05%–1.45%, confidence interval [CI]: 95%). In the control group the loss rate was 0.65% giving a procedure related fetal loss rate of 0.6% which was not found to be a statistically significant difference. Delivery before the 28 th , 32 nd , 34 th , and 37 th week in the study group was reported in 0.2%, 0.8%, 1.2% and 8.1% respectively, and it was not statistically different from controls. Conclusion: The present study has shown that the risk of miscarriage that can be attributed to amniocentesis in our institution is 0.6%, and this is not statistically significant when compared with cases without any invasive procedure during pregnancy. Similarly, the risk for preterm labor was not statistically significant when compared with controls.

Objective: Nonimmune hydrops fetalis (NIHF) is one of the most difficult problems related to pregnancy. The aim of this study was to evaluate the etiological analysis as well as the fetal and neonatal outcomes of NIHF. Methods: We reviewed the prenatal sonographic data and postnatal medical records of pregnant women diagnosed as NIHF in our hospital between January 2001 and May 2013. All cases were categorized using 12 etiological classification groups. Demographic data, diagnostic laboratory parameters, karyotyping results, sonographic and autopsy findings, postnatal final diagnoses, and perinatal mortality rates were also recorded. Results: This study included 147 cases. The mean gestational age at the time of the initial diagnosis was 23.84±6.30 weeks. Cardiovascular causes were the most common (21.7%), followed by structural abnormalities (17.0%), chromosomal abnormalities (6.8%), and skeletal dysplasias (5.4%). Chromosomal abnormalities were detected in 12.8% of these cases. The most common karyotype abnormality was monosomy X. Postmortem autopsy was performed in 50 (34%) cases, and at least one finding was detected in 40 (80%) of these cases. The overall mortality rate was 78.2%. The gestational week at delivery, birth weight, and Apgar score (1 st and 5 th min) showed a statistically significant difference between exitus and surviving fetuses (P<0.05). Conclusion: NIHF can lead to high perinatal morbidity and mortality, yet its etiopathology remains poorly understood. Early diagnosis of NIHF gives parents an opportunity to make an informed choice about the possible complications of a pregnancy.

Background: Multiple first trimester aneuploidy sonomarkers have been introduced recently. Objective: To evaluate the efficacy of first trimester sonomarkers in fetal aneuploidy detection without serum markers. Methods: There were entirely 280 fetuses with 11–13+6 weeks’ gestation (crown-rump -length between 45–84 mm) enrolled to assess nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow. The performance of each single marker and multiple markers for major fetal aneuploidy screening were determined. Results: Totally, 190 fetuses (67.85%) underwent invasive prenatal diagnosis with 14 major chromosome abnormalities identified including 4 cases of trisomy 21, 4 cases of trisomy 18, 3 cases of trisomy 13 and 3 cases of 45, XO. NT was the most accurate single marker with sensitivity of 71.43% and false-positive rate (FPR) of 4.14% while NB or TR was the most specific marker (99.6%) but lacked sensitivity. Among multiple first trimester-screening sonomarkers, NT plus TR evaluation were the most sensitive test (78.57%) with FPR of 4.76%. Conclusion: NT was the most accurate first trimester-screening marker for fetal aneuploidy. NT plus TR assessment as double-screening markers could improve the sensitivity by 7% leading to the lower number of unnecessary invasive prenatal diagnosis.

Background: Periventricular white matter damage (PWMD), also termed periventricular leukomalacia, is the predominant neurologic lesion in preterm infants. It appears to relate in part to the development of the vascular supply to the cerebral white matter. We investigated whether, in case of severe hypoxia-ischemia, the vascular system would be subject to severe damage or remodeled. Aims: To evaluate microvessel density (MVD) and the use of ephrinB2 and its receptor EphB4 to mark arterioles and venules to establish the correct anatomic assignment of the remodeled vessels in a hypoxia-induced PWMD rat model. Methods: Postnatal day 3 rats underwent permanent ligation of the right common carotid artery followed by 6% O 2 for 4 h (hypoxia-ischemia) or sham operation and normoxic exposure (sham). MVD and levels of ephrinB2 and EphB4, which are respectively regarded as relatively specific molecular markers of arteries and veins, were determined at postnatal day 7. Results: Compared with sham rats, MVD, ephrinB2 and EphB4 levels were higher in the brains of hypoxic-ischemic rats. Similar percentages of vessels expressed ephrinB2 and EphB4 in sham rats, but expression of ephrinB2 was greater in brains injured by hypoxia-ischemia. Conclusions: Following hypoxic-ischemic injury to the rat brain, microvessels were remodeled and more arterioles than venules were acquired.