Volume 37, Issue 5

Congenital cytomegalovirus (CMV) infection occurs in 0.6–0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance, with onset or first recognition during pregnancy. The prevalence of GDM, and the occurrence of related complications, depends upon the definition of normal glucose values during gestation. The diagnostic criteria for GDM are controversial mainly because they lack correlation to outcome, be it maternal or perinatal. To date, there are no risk based guidelines to make the diagnosis of GDM and determine practice guidelines that are extrapolated from perinatal and maternal outcome and endpoints. To answer some of the above-mentioned controversies, the hyperglycemia and adverse pregnancy outcome study (HAPO) was planned and executed. This review outlines the results of the HAPO study, which demonstrates that fasting glucose levels and post 75 g OGTT are correlated to maternal, perinatal and neonatal outcomes. It is anticipated that the international recommendation for GDM diagnosis, will be shortly published.

The technology of intrapartum surveillance made rapid strides from the 1960s through the 1980s but then stagnated as increasing resort to caesarean section was made rather than improving measures of fetal condition and labour progress. However, despite caesarean section rates commonly over 30%, medicolegally expensive mistakes continue to be made because it is difficult to teach clinicians to make reliable use of existing technology. It may be that as with aircraft navigation, the safest solution is to replace human judgement with the obstetric equivalent of automatic pilots.

Viability means “the quality or state of being able to live, grow and develop.” Limit of viability has been changed along with the advancement of perinatal and neonatal medicine. The viability limit defined in the Japanese Motherhood Protection Act was amended from 24 to 22 completed weeks of gestation in 1991 based on the survival rate of extremely preterm infants. Survival rates of infants at 22 and 23 weeks' gestation born between 2002 and 2004 in Japan were 31% and 56%, respectively. Though medical data are the most important means to define viability, socio-economical and ethical factors should be also considered, especially when we discuss the group of marginally viable infants. We think there are two different categories of viability limits, one from biological survival limit and another from social agreement of providing active medical intervention. Currently in Japan, the former viability definition based on purely medical data is 22 completed weeks and the latter definition is the social consensus of about 24–28 weeks' gestation.

There is a world-wide interest in outpatient care. Induction of labor is commonly offered to women with prolonged pregnancy, and evidence from randomized controlled studies suggest that inpatient and outpatient induction achieve comparative maternal and fetal outcomes. However, safety data are very limited. Careful selections of appropriate patients as well as standardized monitoring protocols are essential before outpatient induction can be initiated. Uterine hyperstimulation with fetal heart rate deceleration and other maternal or fetal adverse events are rare but unpredictable. Unrecognized fetal hypoxia due to uterine contractions remains an unsolved problem after discharge from the hospital. The ideal method for outpatient cervical ripening is controversial. The local application of nitric oxide donors prior to induction might be a promising approach. Larger studies are necessary before widespread use of outpatient cervical ripening by prostaglandins or other cervical ripening agents can be advocated.

A progressive insulin resistant state develops throughout human pregnancy. Inositol phosphoglycan P-type (P-IPG), a second messenger of insulin, was reported to negatively correlate with the degree of insulin resistance in non-pregnant diabetic subjects. Urinary levels of P-IPG were assessed in insulin resistant states during pregnancy such as gestational diabetes mellitus (GDM, n=44) and type 2 diabetes mellitus (type 2 DM, n=25) and in 69 normal pregnant women. Urinary levels of P-IPG were higher in GDM than controls with a positive trend of release throughout normal pregnancy (P<0.01). P-IPG excretion was higher in diabetic (GDM and type 2 DM) than in healthy women in the second trimester (P<0.05). A higher P-IPG urinary excretion occurs during the second trimester in pregnant women with clinically evident insulin resistance with a positive association with poor glycemic control.

Objective: To determine pregnancy outcome in patients with short cervix on transvaginal ultrasound between 16 and 24 weeks' gestation treated with McDonald cerclage compared to weekly intramuscular injections of 17 α-hydroxyprogesterone caproate (17OHP-C). Methods: From November 2003 through December 2006, asymptomatic, singleton pregnancies were screened with transvaginal ultrasound between 16–24 weeks' gestation. Patients with a cervical length (CL) ≤25 mm were offered enrollment. Patients were randomly assigned to treatment with McDonald cerclage or weekly intramuscular injections of 17OHP-C. The primary outcome was spontaneous preterm birth (PTB) prior to 35 weeks' gestation. Results: Seventy-nine patients met inclusion criteria; 42 were randomly assigned to the cerclage and 37 to 17OHP-C. Spontaneous PTB prior to 35 weeks' gestation occurred in 16/42 (38.1%) of the cerclage group and in 16/37 (43.2%) of the 17OHP-C group (relative risk, 1.14 95% CI, 0.67, 1.93). A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB <35 weeks between groups. A similar analysis of patients with a CL≤15 mm showed a reduction in spontaneous PTB <35 weeks in the cerclage group (relative risk 0.48, 0.24–0.97). Conclusion: Women with CL ≤25 mm in the second-trimester appear to have similar risks of delivering prior to 35 weeks' gestation when treated with 17OHP-C or McDonald cerclage. However, cerclage may be more effective in preventing spontaneous PTB in women with CL≤15 mm.

Aim: To study the relation of umbilical cord insertion (CI) site in early gestation and placental development from the chorion villosum. Methods: We ultrasonically measured the distance between the internal cervical Os and the CI site (CID), the distance between the internal cervical Os and lower placenta edge (PLD), and placental thickness at early (10–12 weeks) and mid-gestation (18–20 weeks). Results: CID in early gestation (CID-Early) correlated with CID in mid-gestation (r 2 =0.171; P<0.01). CID-Early correlated with PLD in mid-gestation (r 2 =0.093; P<0.01). Thickness of chorion villosum or placenta in early gestation did not correlate with that at mid-gestation. Increasing thickness of placenta was significantly higher in long CID-Early (≥20 mm) cases than short cases (<20 mm) (P<0.05). Conclusions: The process of placental development and the placental location are affected by CI location at early gestation, and suggests that this process might be affected by poor blood supply from the low uterine segment when CI site is close to the internal cervical Os.

Objective : The 2002 CDC guidelines for the prevention of perinatal group B streptococcus (GBS) stipulate that vancomycin is reserved for penicillin-allergic women at high risk for beta-lactam anaphylaxis with resistance to clindamycin or erythromycin. Our objective was to evaluate practitioner adherence to these guidelines. Methods : This is a retrospective chart review of patients admitted to labor and delivery who received vancomycin for GBS prophylaxis from January 1st, 2005 to June 1st, 2007. Identification and documentation of allergic reactions to beta lactams and performance of GBS sensitivities at the time of screening were recorded. Results : Eighty-seven patients reporting a penicillin allergy received vancomycin during labor. In 71 patients screened at 35–37 weeks, sensitivities were not performed for 55 patients, of which 10 reported an anaphylactic-like reaction to penicillin. Of 15 patients who had sensitivities performed at the time of screening and were resistant to clindamycin and/or erythromycin, only two patients, however, described an anaphylactic-like reaction to penicillin. Fourteen patients received vancomycin due to an unknown GBS status at <35 weeks of gestation and only three patients from this group reported an anaphylactic-like reaction to penicillin. There were deviations from the CDC protocol in 82 (94%) of 87 patients who received intrapartum vancomycin there were deviations in the CDC protocol. Conclusion : Most patients receiving intrapartum vancomycin for perinatal GBS prophylaxis either did not have a culture with sensitivities performed at the time of GBS screening due to a history of anaphylactic-like reactions to penicillin or received vancomycin for a mild or unknown allergy. Physician adherence to the CDC guidelines with regards to the use of vancomycin is far from optimal.

Aim : Serum osteocalcin was shown in a previous study on first trimester pregnant women to correlate with bone density and to distinguish between fast and slow bone losers. The objective of the present study is to examine whether serum osteocalcin is related to vitamin D receptor (VDR) BsmI polymorphism in pregnant women. Study design : We determined osteocalcin serum levels and VDR BsmI genotype in 97 healthy first trimester pregnant women consecutively recruited during six months. Results : BB (21%), Bb (38%) and bb (41%) genotypes showed similar osteocalcin serum levels. However, in primigravidas (n=38) the BB genotype was significantly associated with higher mean osteocalcin level (9.67 ng/mL) than the Bb (8.07 ng/mL) and the bb genotype (8.14 ng/mL), respectively (P<0.05). The VDR genotype was the only independent parameter to correlate with serum osteocalcin (P<0.05). Conclusion : Only primigravidas show in the first trimester a relation between the bone formation parameter serum osteocalcin and the VDR genotype BB which indicates a higher risk of fractures. For further clinical applications serum osteocalcin and VDR genotype should be tested on a cohort of primigravidas including measurements of bone density.

Aim : We evaluated variations in behavior of arylsulphatase A activity (an enzyme that catabolizes sulphatides) and of sulphatide concentration in the placenta, cord and membranes of healthy gravidas at term pregnancy, following spontaneous birth. Methods : We extracted and biochemically determined arylsulphatase A and sulphatide concentration in placenta, cord and membranes (far from and close to internal uterine os) in 14 patients. Results : Activity of arylsulphatase A decreased in the cord, in membranes far from the internal uterine os, in membranes close to the internal uterine os and in the placenta. Sulphatide concentration was minimal in the cord and maximal in placenta, with intermediate values in the membranes. No correlation was found between arylsulphatase A activity and sulphatide concentration, nor among arylsulphatase A activities, nor among sulphatide concentrations among the different tissues. It seems that multiparity may increase and the duration of active labor may decrease arylsulphatase A activity in membranes far from the internal uterine os, while active labor duration does not appear to have any implication on sulphatide concentration in membranes close to the internal uterine os. Conclusions : Arylsulphatase A activities and sulphatide concentrations in fetal adnexa show significant differences.

Objective: Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design: This cross-sectional study included 486 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=48) and without (n=45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n=152); b) PTL without IAI who delivered preterm (<37 weeks gestation; n=107); and c) PTL with IAI (n=82). Ang-2 concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analysis. Results: 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P<0.001); 3) among patients with PTL, the median AF Ang-2 concentration was significantly higher in patients with IAI than in those without IAI (4031.3 pg/mL vs. 2599.4 pg/mL; P<0.001) and those with PTL without IAI who delivered at term (4031.3 pg/mL vs. 2707.3 pg/mL; P<0.001); and 4) no significant differences were observed in the median AF Ang-2 concentration between patients with spontaneous labor at term and those at term not in labor (1722.9 pg/mL vs. 1877.4 pg/mL; P=0.6). Conclusions: 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation.

Aim : To establish the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers delivering babies at term. Methods : A total of 148 mothers delivering babies at term were recruited from Bharati Medical Hospital, Pune, India. Results : Levels of DHA and AA in both plasma and erythrocyte were higher in cord blood compared to levels in maternal blood (P<0.001). Maternal plasma and erythrocyte DHA levels had a positive association with the respective levels in cord blood (P<0.001). However, such an association was not seen for AA levels. Maternal plasma omega 3 and omega 6 fatty acids were positively associated with the respective milk fatty acids (P<0.01). Conclusions : Our results indicate that milk long-chain polyunsaturated fatty acids (LCPUFA) status reflects the concentrations of maternal LCPUFA in women delivering babies at term. Improving the maternal LCPUFA status throughout pregnancy and lactation may improve the milk LCPUFA status and ultimately benefit the infant.

Aims: To evaluate the predictive value of body mass index (BMI), Bishop score, and sonographic measurement of cervical length for predicting successful labor induction (defined as an ability to achieve the active phase of labor corresponding to a cervical dilatation of ≥4 cm within 12 h of initiating oxytocin) in near-term twin gestations. Methods: This prospective, observational study enrolled 72 consecutive women with twin gestations at >36.0 weeks' gestation who were scheduled for induction of labor. Transvaginal ultrasound for measurement of the cervical length was performed and the Bishop score was determined by digital examination. The BMI was calculated based on the weight and height at the time of induction. Results: Labor induction was successful in 63% (45/72) of women. The mean BMI was significantly lower in women who had successfully induced labor, but no significant differences existed with respect to the mean cervical length, median Bishop score, proportion of parous and nulliparous women, and the mean total birth weight of the twin pairs between the two patient groups. Multiple logistic regression demonstrated that only BMI provided a significant contribution in predicting successful labor induction. Conclusions: BMI independently predicted the success of labor induction in twin gestations but the sonographic measurement of the cervical length and Bishop score had poor predictive values for successful induction.

Objective: To compare selected umbilical cord parameters, especially cord coiling, between breech and vertex presentations. Methods: We prospectively collected umbilical cords from uncomplicated breech and vertex obtained during elective term cesarean deliveries. We compared various cord parameters between the two groups as well as data regarding obstetric history and pregnancy outcome. Results: We evaluated 55 umbilical cords from breech and 55 from vertex deliveries. Umbilical cord length (56.93 cm vs. 63.95 cm, P=0.05), number of coils (5.1±0.4 vs. 11.7±0.6, P<0.0001) and umbilical cord index (UCI) (0.09 coils/cm vs. 0.18 coils/cm, P<0.0001) were all significantly lower for breech presentations and remained significant following multivariate analysis. Conclusion: We document significant differences in umbilical coiling and the UCI between breech and vertex presentation. The precise reason for these differences is still unclear.

Objective : To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. Patients and methods : From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player ® , STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. Results : There was no correlation between STV and fetal scalp pH measurements (r=−0.0592). Conclusions : Fetal STV is an important parameter with high sensitivity for antenatal fetal acidosis. This study shows that STV calculations do not correlate with fetal scalp pH measurements during labor, hence are not helpful in identifying fetal acidosis.

Background: Meconium peritonitis (MP) is a rare prenatal condition that leads to substantial neonatal morbidity and mortality. Patients and methods: All patients between 1998 and 2006 referred for prenatal diagnosis were retrospectively analyzed for diagnosis of MP. Prenatal ultrasound findings were compared with postnatal etiology, intraoperative findings, and postnatal outcome of the patients. Results: Antenatal MP was diagnosed in 14 fetuses between 18 and 38 weeks' gestation. The prenatal diagnosis of MP was confirmed by clinical and radiological findings in 8 (62%) of 13 infants born alive. All patients were delivered preterm between 33 and 36 weeks' gestation by cesarean section. Urgent neonatal surgery for treatment of bowel obstruction was required in all eight infants. Prenatal ultrasound diagnosis of bowel dilatation was the only variable found to be associated with the need for subsequent surgical intervention (P=0.02). Conclusions: Clinical outcome of MP diagnosed antenatally can be either mild or severe form. The underlying cause of severe MP is heterogeneous and neonatal surgery was always required.

Aim: To assess reasons for higher levels of anxiety generated by prenatal counselling of a condition with good outcome such as cystic adenomatoid malformation (CCAM) of the lung compared to a life-threatening malformation such as congenital diaphragmatic hernia (CDH). Materials and methods: The Spielberger State-Trait Anxiety Inventory (STAI-S) was used to measure anxiety in two groups of mothers carrying a fetus with the respective malformation. Results: Forty-four mothers completed the questionnaire (CCAM, n=21 and CDH, n=23). Before consultation, the mean STAI-S scores in the CCAM group (44.80±5.92) and in CDH group (44.05±4.96) were not significantly different but was significantly reduced in both groups after consultation (CCAM 44.80 vs. 41.60, P=0.014 and CDH 44.05 vs. 34.35, P=0.0001). The groups were not significantly different regarding gestational age at diagnosis. Conclusions: After initial prenatal counselling, uncertainty about prenatal outcome and lack of defined management plans in CCAM seems to be more important than higher mortality rate occurring in CDH.

Objective : The fetal inflammatory response syndrome (FIRS) is present in a fraction of fetuses exposed to intra-amniotic infection and is associated with the impending onset of labor and multisystem organ involvement. Neonates born with funisitis, the histologic counterpart of fetal systemic inflammation, are at increased risk for cerebral palsy and bronchopulmonary dysplasia. The aim of this study was to determine whether fetal and maternal granulocytes and monocytes have the phenotypic and metabolic characteristics of activation in cases with FIRS. Study design : A case-control study was conducted with umbilical cord and maternal blood samples obtained from patients who delivered preterm with (n=30) and without funisitis (n=15). The phenotypic characteristics of granulocytes and monocytes were examined using flow cytometry and monoclonal antibodies including CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were measured at the basal state and after stimulation (oxidative burst). A P<0.01 was considered statistically significant. Results : (1) Funisitis was associated with a significant increase in the median mean channel brightness (MCB) of CD14, CD64, and CD66b on granulocytes and the MCB of CD64 on monocytes collected from umbilical cord blood. (2) The basal iROS production and oxidative burst were higher in the umbilical cord monocytes of neonates with funisitis than in those without funisitis. (3) There were no differences in the immunophenotype, basal iROS production, and oxidative burst in maternal granulocytes or monocytes between the study groups. Conclusion : Fetal systemic inflammation is associated with phenotypic and metabolic changes consistent with activation in fetal immune cells but not in maternal blood.

Brain-derived neurotrophic factor (BDNF) is highly expressed in the developing brain. It has anti-apoptotic abilities, and protects the neonatal brain. In experimental settings in adult animals, pre-treatment with nicotine has shown increased BDNF levels, indicating a possible contribution to nicotine's anti-apoptotic effect. Apoptosis contributes to the development of brain damage in perinatal asphyxia. We examined the effects of nicotine on apoptosis-inducing factor (AIF), caspase-3 and BDNF in the hippocampus of a neonatal piglet model of global hypoxia. Forty-one anesthetized newborn piglets were randomized to one of four groups receiving different infusions after hypoxia (1) nicotine 130 μg/kg/h, 2) 260 μg/kg/h, 3) adrenaline, and 4) saline, all 2.6 mL/kg/h. Four hours after hypoxia they were euthanized. The left hemisphere/hippocampus was examined by histopathology and immunohistochemistry; the right hippocampus was analyzed using real time PCR. There was a significantly higher expression of BDNF mRNA and protein in the animals treated with nicotine 130 μg/kg/h vs. the saline treated group (mRNA P=0.038; protein P=0.009). There were no differences regarding AIF or caspase-3. We conclude that nicotine (130 μg/kg/h), infused over 1 h after global hypoxia in neonatal piglets, increases levels of both BDNF mRNA and protein in the hippocampus. This might imply neuroprotective effects of nicotine in asphyxiated neonates.

Objectives: To examine whether exogenous pulmonary surfactants (exPS) substitute for or merely supplement endogenous pulmonary surfactants (enPS) by looking at sequential changes in the surfactant proteins (SP) SP-A and SP-D in alveolar pools. Methods: Fourteen preterm infants with RDS treated with an artificial surfactant were compared to five normal-term infants without RDS who were treated with artificial ventilation at birth. Results: Immediately after birth, SP-A and SP-D were essentially absent in the alveolar pools of the RDS group, but were present at normal levels in the controls. Treatment with exPS apparently stimulated enPS production. Conclusions: In infants who responded well to exPS therapy, the SP concentration reached essentially normal levels within 48–72 h after birth.

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