Volume 33, Issue 2

Obesity has become a major health problem all over the world and during pregnancy is associated with an increased risk of complications, including gestational diabetes, preeclampsia, and delivery complications such as macrosomia, shoulder dystocia and higher rates of cesarean sections and infections. Maternal obesity may also be an independent risk factor for neural tube defects and fetal mortality. This review focuses on the consequences of maternal obesity during pregnancy.

The request for cesarean section without medical indication has become one of the dilemmas faced by the obstetrician. Most recent studies that compare vaginal delivery with elective cesarean section find them equally safe. This comparison is lacking in the option of trial of labor, which may result in an assisted vaginal delivery or intrapartum cesarean section, both with increased morbidity and mortality for the mother and newborn. When considering elective cesarean section, the obstetrician has to take into account improved anesthetic techniques and the decrease in morbidity and mortality after cesarean section with the trend toward patient autonomy to decide on her own treatment. On the other hand, the obstetrician has to advise his patient of the best treatment with respect to possible complications in future pregnancies, such as placental complications and increased morbidity and mortality resulting from repeated cesarean sections. The advantage of cesarean section for pelvic floor protection does not exist after three consecutive cesarean sections and equals the rate of urinary incontinence after consecutive three vaginal deliveries. In countries such as ours, where most women wish for several children, the risk-benefit balance is toward repeated spontaneous vaginal deliveries.

We analyzed a cohort of 2850 live-born triplet sets to compare age, parity, stature, pre-gravid body mass index (BMI), and weekly weight gain in mothers who delivered triplets with a total weight in the 10th, 5th, and 1st deciles corresponding to the heaviest, average-weight, and lightest triplet sets, respectively. Mothers who delivered the heaviest triplets were significantly older, multiparous, taller, heavily built, and gained more weight compared with mothers of average-weight triplets. In contrast, except for higher parity, mothers of average-weight sets were not significantly different compared with mothers who delivered the lightest triplet sets. We concluded that parity was the only significant factor for increased total triplet weight in the first five deciles. However, the presence of other factors in addition to parity is needed for a triplet pregnancy to be included in the 10th decile.

Aim : To examine the gestational age-specific distribution of twin birth weight discordance. Methods : We analyzed all liveborn twin sets between 28 and 40 weeks' gestation from the United States 1995–1998 Multiple Matched Birth Data Set compiled by the National Center for Health Statistics. We calculated the 50th and 95th percentiles of birth weight discordance at each gestational age. Neonatal mortality rates were calculated for discordant twins at the 95th percentile of birth weight discordance for each gestational age. Results : At older gestational ages, the 95th percentile of birth weight discordance resulted in an inter-twin birth weight difference of approximately 25%, a value often used to define twins as birth weight discordant. However, at earlier gestational ages, the 95th percentile of birth weight discordance was greater, reaching nearly 50% at 28 weeks. Conclusions : The inter-twin birth weight difference at the 95th percentile is greater at lower gestational ages, possibly illustrating the different nature or severity of twin birth weight discordance at an earlier gestational age.

Objective : The purpose of this study was to evaluate the levels of amino-terminal probrain natriuretic peptide (Nt pro-BNP) in preeclampsia in comparison with normotensive pregnancy. Materials and methods : Women with preeclampsia (proteinuria ≥300 mg/24 h and at least two readings of systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥90 mm Hg) (n=32 mild preeclampsia and n=8 severe preeclampsia) were compared with normotensive women (n=40). Serum Nt pro-BNP was measured using an electrochemiluminescence immunoassay (ECLIA) method (Nt pro-BNP, Roche) with a Roche modular analytics E170 immunoassay analyzer. Statistical analysis was carried out by the Student t-test, and a P value of <0.05 was accepted as statistically significant. Results : The median serum Nt pro-BNP was 430±28.91 pg/mL in preeclampsia. The levels of serum Nt pro-BNP were 74±16.82 pg/mL in normotensive pregnant women (P<0.001) and significantly higher in women with preeclampsia (P<0.001). Conclusion : The higher levels of serum Nt pro-BNP in preeclamptic women may be an indicator of high left-ventricular filling pressure, and indicate left-ventricular diastolic dysfunction.

Objective : Using the Continuous Glucose Monitoring System (CGMS ® ; Medtronic Minimed) for a group of pregnant women with and without glucose intolerance, we attempted to answer the following questions: (1) when does the physiological peak of postprandial glucose occur?; (2) do non-diabetic pregnant women and pregnant women with diabetes have different postprandial glucose profiles?; and (3) what is the optimal time for postprandial glucose measurement rated according to clinical outcome? Methods : We included 53 pregnant women in our study. Based on the criteria of the German Diabetes Association (fasting, 5.0 mmol/L; 1-h, 10.0 mmol/L; 2-h, 8.6 mmol/L) we included 13 women with gestational diabetes, four with type 1 diabetes and 36 non-diabetic pregnant (NDP) women. Gestational and type 1 diabetics were classed as one group: pregnancy complicated by diabetes (PCD). Patients with carbohydrate intolerance underwent dietary counseling in accordance with the recommendations of the American Diabetes Association. Patients received a CGMS ® for use over 72 h. This was calibrated seven times a day with an Accu-Check ® . The pre- and postprandial glucose levels were documented at 15-min intervals for 3 h from the beginning of each meal. The postprandial data from the three meals were added. The group was divided according to three clinical outcome parameters: mode of delivery, birth weight percentile, and diabetes-associated complications. Results : Statistically significant differences between groups were found for body mass index, fetal birth weight and oral glucose tolerance test. No significant differences were found for age, parity and gestational age, mode of delivery, and diabetes-associated complications. The sensor provided similar numbers of measurements in both groups (278±43 vs. 298±73, P=0.507). The postprandial glucose peak was reached after 82±18 min in the non-diabetics vs. 74±23 min in the PCD group (not significant). Postprandial glucose values were normally slightly higher in PCD (not significant). We added the postprandial glucose values at each time interval for the three meals for each day. For the sum, there was a significant difference between the measurements at 120 min and at 135 min postprandial (P<0.05). Dividing the group by clinical outcome showed a significant difference between the postprandial time intervals of 75 min and 105 min (P<0.05). In addition, the time interval was different from 60 min to 135 min for the mode of delivery and birth weight percentile (P<0.05). Conclusion : The 120-min interval is too long and has a lower correlation to clinical outcome parameters than earlier measurements. Our findings show that the optimal time for testing is between 45 and 120 min postprandial. Based on our practical experience and dietary recommendations, we would prefer a 60-min interval, because patients can calculate this more easily and can have more freedom to eat the recommended number of snacks.

Objectives: To assess by two- and three-dimensional ultrasound the diameter and volume of the yolk sac in pregnant women affected by type 1 diabetes during the first trimester of pregnancy. Methods: 18 women affected by insulin-dependent diabetes mellitus (IDDM) and 52 normoglycemic pregnant women (controls) were enrolled in this study. The women were evaluated once a week (5–12 weeks of pregnancy). Ultrasound examination in all pregnant women was initially performed in a bidimensional fashion with a transvaginal 6.5-MHz probe and subsequently using a three-dimensional technique. Results: In the pregnant diabetic women the diameter of the yolk sac was significantly higher than that of controls in the first weeks of pregnancy, reaching a maximum diameter at 9 weeks, and decreasing thereafter, earlier than controls. The volume of the yolk sac increased in both groups from 5 weeks of pregnancy and reached maximum values at 10 weeks in both groups. The volumetric increase and decrease after reaching highest values were greater in IDDM patients. Conclusion: The clinical and diagnostic implications of the results of this study are still to be defined. Such a diagnostic technique may prove to be an additional element in monitoring diabetic women during early pregnancy.

Aims : Cellular turnover may be involved in remodeling of the cervix during parturition. Therefore, the number and localization of apoptotic and proliferating cells during cervical dilatation at term were determined. Methods : Biopsy specimens from the lower uterine segment of 36 women undergoing cesarean section with a cervical dilatation of <2 cm (n=10), 2–<4 cm (n=9), 4–6 cm (n=8), and >6 cm (n=9) were examined for nuclear fragmentation by the TUNEL assay, and for cell survival by the apoptosis-blocking bcl-2. Proliferation was marked by Ki-67, epithelial cells by cytokeratin and leukocytes by CD 45. For quantification of apoptotic and proliferating cells, eight random fields of each specimen stained for TUNEL or Ki-67 were blindly counted by two investigators. For statistical evaluation, 90% confidence intervals based on a Poisson distribution were used; groups with non-overlapping intervals were considered significantly different. Results : Apoptotic cells were found exclusively within the stromal compartment, while bcl-2 was expressed in epithelial cells and leukocytes. Proliferating cells were of stromal and epithelial origin. The number of apoptotic as well as proliferating cells ranged from 0 to 2 cells per high-power field (median number 0) in all groups. The confidence intervals were overlapping for all groups, showing no statistical difference between them. Conclusion : Apoptosis does not seem to play a decisive role in the process of cervical dilatation during parturition at term.

Objective : Soluble vascular cell adhesion molecule-1 (VCAM-1) is known to be elevated in serum of patients with preeclampsia, but there are no data available on the significance of urinary VCAM-1 excretion in preeclampsia. The aim of our study was to uncover possible circadian rhythms of VCAM-1 plasma levels and urinary VCAM-1 excretion in uncomplicated and hypertensive pregnancies and to ascertain their relation to blood pressure. Study design : A total of 10 normotensive and 10 preeclamptic pregnant women were included in this study. Venous blood was collected hourly, and urine samples were taken every 2 h over a period of 24 h. VCAM-1 levels were determined by ELISA. We compared these results with the circadian blood pressure rhythm. Results : The median VCAM-1 plasma levels were significantly (P<0.01) increased in preeclamptic patients (851.5 ng/mL) in comparison to normotensive pregnant women (659.3 ng/mL) without any circadian rhythm being apparent; however, the urinary excretion of VCAM-1 showed a typical circadian rhythm, with a higher excretion rate during daytime. Conclusion : For the first time we have demonstrated that urinary VCAM-1 excretion in pregnancy shows a circadian rhythm without correlation to plasma levels or the circadian blood pressure rhythm. In contrast, VCAM-1 serum levels did not show a diurnal rhythm. We assume that VCAM-1 serum levels do not correlate with systemic blood pressure or urinary excretion.

Aim : To investigate the influence of maternal and cord serum and amniotic fluid growth hormone (GH) and insulin and other neonatal and maternal factors on birthweight. Methods : A total of 160 pregnant women at 38–42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n=50), large for gestational age (LGA) (n=50) or average for gestational age (AGA) (n=60). GH and insulin levels were measured in maternal and cord serum and amniotic fluid at birth. Results : GH levels in maternal and cord serum and amniotic fluid showed no differences among the three weight groups (P>0.05). The cord insulin level was significantly lower in SGA (P<0.01). The insulin level in venous cord blood correlated with birth and placental weights and neonatal height, whereas maternal serum and amniotic fluid insulin levels, and maternal and cord serum and amniotic fluid GH levels did not show any correlation with birthweight. The cord GH level at birth was correlated with GH levels after 4 postnatal weeks in the SGA group (P<0.01). In addition, birthweight showed a correlation with prepartum maternal weight, maternal weight gain, maternal height, neonatal length and placental weight in all three weight groups. Conclusions : Cord GH, maternal serum and amniotic fluid GH and insulin levels did not correlate with birthweight in all three weight groups. The lack of correlation for GH levels in maternal and cord serum and amniotic fluid suggests that these compartments may be non-communicating separate units.

Aim : To reassess the cut-off value for lamellar body counts (LBs) for fetal lung maturity (FLM) over a 10-year study period. Patients and methods : 178 pregnancies were selected under strict inclusion criteria and delivered within 48 h from amniocentesis. FLM was determined by amniotic fluid LBs in centrifuged samples (300× g for 10 min) in a commercially available Coulter Counter. Cases beyond 37 weeks were excluded. Results : Mean gestational age was 33.5±3.0 weeks at amniocentesis and 33.7±3.0 weeks at birth. After reassessing the best compromise between sensitivity and specificity for all cases using the receiver operating characteristic (ROC) procedure, an FLM cut-off value of ≤22,000/μL was obtained. Diagnostic accuracy (and confidence interval, CI) was: sensitivity, 73% (60.0–83.6%); specificity, 81.7% (CI 73.6–88.1%); positive predictive value, 66.2%; and negative predictive value, 86.0%. Conclusion : No significant change in FLM cut-off for LBs was found when comparing the value from this study and the results of our earlier report presented in 1996 (≤22,000 vs. ≤20,000/μL), although the new value may be more accurate, since it is based on neonatal outcome with the exclusion of cases in which the diagnosis of FLM is seldom warranted, i.e., >37 weeks' gestational age.

Objective : The purpose of our study was to compare clinical criteria with echocardiographic findings in diagnosing hemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Methods : We evaluated 25 preterm infants born at 24–32 weeks of gestation with birth weight from 500 to 1700 g for tachycardia, heart murmur, hyperdynamic chest, presence of dorsalis pedis pulse, hypotension, and worsening of the respiratory status at 48–72 h of life. A pediatric cardiologist blinded to clinical findings performed the echocardiograms. Infants with congenital anomalies and conditions, sepsis, IVH, and necrotizing enterocolitis were excluded. Results : Out of 25 preterm infants, 12 infants had hemodynamically significant PDA with left-to-right shunt. Two infants had small PDA and in 11 infants the ductus arteriosus was not patent. PDA infants had lower gestational age (P=0.02) and birth weight (P=0.03). Their Apgar scores (1 min) were lower (P=0.03). The heart rate between the two groups differed, but was clinically within normal limits. Systolic (P=0.05) and mean blood pressures (P=0.04) were lower in the PDA group. A poor association between heart murmur, hyperdynamic chest and dorsalis pedis pulse, and the presence of PDA was revealed. Conclusion : Echocardiogram is required for early diagnosis of PDA in preterm infants, as clinical signs are not reliable in the first few days of life.

Sudden infant death syndrome (SIDS) “gray zone” or borderline cases are defined as those cases in which it is difficult to establish whether the pathological findings are sufficiently severe to have caused the death. Examination of the brainstem in 103 cases of SIDS disclosed five SIDS “gray zone” cases in which only further investigations of serial sections successfully identified anatomico-pathological findings that likely represent the morphological substrates for a sudden reflexogenic death. A complete autopsy was performed, including close examination of the brainstem and cardiac conduction system, according to our guidelines. Our five cases are consistent with the triple-risk model of SIDS, a hypothesis postulating an underlying biological vulnerability to exogenous stressors or triggering factors in a critical developmental period. Inflammatory infiltrates (cases 1 and 2), necrotic focus of the solitary tract (case 3), hemangioendothelioma (case 4) and mild pneumonia (case 5) alone might or might not have accounted for the sudden deaths, if it had not been for the location and/or concomitant presence of brainstem abnormalities that could have had a triggering role in causing the sudden death of these babies.

Aims : Magnetic resonance imaging (MRI) is accepted as the gold standard for the diagnosis of arterial cerebral infarction (ACI), but few studies have reported the incidence of neonatal ACI based on MRI findings. We provide new population-based epidemiologic and diagnostic data on all infants diagnosed between 1997 and 2002 in our center with an MRI-confirmed diagnosis of unilateral neonatal ACI. Results : Nine patients were identified, giving an incidence of 1:2300 unilateral ACIs in our inborn population. In all patients the middle cerebral artery was affected. Seven patients showed epileptic seizures, usually starting within the first 3 days of life. EEG was pathologic in all patients. Only three infarctions were diagnosed by ultrasound. Initial MRI established diagnosis of ACI in eight out of nine patients and subsequent MRI described the exact location of infarctions in all patients. Six out of nine patients developed hemiparesis and five had deficits in language development. There is a substantial need for special care facilities and long-term therapeutic interventions. Conclusions : The incidence of neonatal ACI is higher than previously reported. The sensitivity of early cerebral ultrasound for diagnosis of ACI is low. Seizures in the first 3 days of life combined with pathologic EEG findings should lead to MRI, regardless of normal cerebral ultrasound.

Aims : Clinical follow-up of possible fetal complications associated with maternal parvovirus B19 infection is usually recommended during the 2–3 months after primary infection. Results : A case of late intrauterine fetal death associated with at least 5 months of maternal parvovirus B19 viremia and in the presence of B19 IgG and IgM is described. Conclusions : The time of clinical and laboratory follow-up after maternal parvovirus B19 infection may need to be revised if prolonged viremia is more common than previously described.

Arthrogryposis may result from various neuromuscular or connective tissue disorders leading to in utero hypokinesia or akinesia and the prenatal development of joint contractures. We report the case of a preterm neonate born with arthrogryposis and flaccid quadriplegia that led to the diagnosis of myopathy with muscle spindle excess. The rare and unusual histopathologic abnormality associated with the myopathy illustrated in this case has been described in only three other cases in the medical literature. The concurrence of hypertrophic cardiomyopathy, arthrogryposis, and myopathy with muscle spindle excess suggests the presence of a newly described syndrome. This case clearly demonstrates that specific prenatal ultrasonographic findings combined with the presenting clinical manifestations should promptly raise the suspicion of a neuromuscular disorder.