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Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n = 6), amniotic fluid (AF, n = 176) and/or fetal blood specimens (n = 80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV-specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n = 24) or in urine of neonates within the first 2 weeks of life (n = 33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live-born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV-DNA and CMV-specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV-DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22-23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p = 0.0224). However, normal ultrasound of infected fetuses at WG 22-23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques.

In Germany, studies on the IgG seroprevalence in pregnancy and in women of childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG seropositive rate in 40,324 pregnant women as well as in 31,093 female and male bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result of a study conducted in 1999 investigating 1,305 healthy adolescents with known ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15-50 years) was 42.3%. Age-dependent analysis revealed a significantly higher seropositive rate (55.6%) in young women (15-25 years) than in those aged 26-40 years (37-42%) and in women older than 40 years (48.3%). Over the study period of 15 years, the rate of seroprevalence in pregnant women declined significantly (χ(2) test < 0.01) from 44.3% in the first interval period (1996-2000), to 42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV seropositivity appeared to be the socioeconomic status (SES), which we characterized by type of health insurance: Seroprevalence in women with low, middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow donors of childbearing age (15-45 years) showed a significantly higher seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents aged 13-16 years, no gender-specific differences were recognized. Concerning ethnicity, youngsters with German descent had a significantly lower seroprevalence (29.9%) than those with non-German descent (67.4%).

Estimation of IgG avidity index is a classical serological method. Antibodies with low avidity are detectable at a very early stage of infection whereas high avidity antibodies indicate past infection. Recently, it was shown that the neutralization assay can be routinely used as a reliable method for differentiating between acute primary and non-primary infection in a single serum sample because the first neutralizing titers (NT) appeared after an average of 13 weeks (range, 10-17 weeks). A low positive NT titer in the presence of specific IgM antibodies, however, still represents a diagnostic problem especially if blood sampling occurred after the 12th week of gestation. To overcome this problem the combination of NT and IgG avidity tests was evaluated. Human cytomegalovirus (HCMV) IgG avidity indices of 350 serum samples from 227 pregnant women were investigated using 6M urea in the washing buffer. HCMV specific IgG antibodies reached full maturation approximately 20-22 weeks after seroconversion and low IgG avidity is therefore a marker of primary infection. The combined application of the microneutralization and avidity assays was shown to serve as a helpful tool in diagnosis of a recent primary HCMV infection of second trimester pregnancy particularly when previous serological data were not available.

Objective To estimate the risk of congenital cytomegalovirus infection and disease following primary maternal infection around the time of conception compared with the risk during later stages of pregnancy. Design Cohort study between 1990 and 2003.Setting Germany.Participants One hundred and sixty-six pregnant women with serologically confirmed primary cytomegalovirus infection and known outcome. Methods Timing of primary cytomegalovirus infection by analysing the kinetics of cytomegalovirus-specific IgG and IgM antibodies, the IgG avidity index and neutralising antibodies. Main outcome measure Onset of maternal primary infection in relation to congenital infection and disease.Results Preconceptional (between eight and two weeks before onset of the last menstrual period) was determined in three women and did not lead to congenital infection. Periconceptional infection (between one week before and five weeks after last menstrual period) occurred in 20 women with congenital infection in nine cases (45%). Timing was less precise (between eight weeks before and five weeks after last menstrual period) in an additional 10 women, three cases of which resulted in congenital infection. Of the 12 pregnancies in which congenital infection occurred, seven were terminated, six before the 12th week of gestation (WG 12) and one at WG 19 due to fetal hyperechogenic bowel. One of the five infected live-born infants delivered to a mother with periconceptional infection showed dystrophy and mild microcephaly at birth, but had a rather normal development at two years of age. Primary infections occurring between WG 6-20 and WG 20 -38 resulted in transmission rates of 30% (27/89) and 58% (18/31), respectively. Conclusions Counselling of women with periconceptional primary cytomegalovirus infection should be adjusted to offer prenatal diagnosis and high-level ultrasound controls due to the considerable risk for fetal infection and uncertainty of clinical outcome and disease.

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An estimated 6% to 8% women develop hypertension during pregnancy, which has been linked with asthma, through either the condition itself or treatment such as oral corticosteroids. Steroid use also has been linked with an increased risk of preeclampsia. This large population-based case-control study was planned to determine whether inhaled steroids increase the risk of either pregnancy-induced hypertension or preeclampsia in asthmatic women. Participants were 3505 women with asthma, 14-44 years of age, who had 4593 pregnancies in the years 1990-2000. As many as 10 control women at 30 or more weeks gestation were selected for each case. Sociodemographic factors were similar in the case and control groups.There were 302 cases of pregnancy-induced hypertension, representing 6.6% of the study population. They included 128 cases of gestational hypertension, 165 cases of preeclampsia, and 9 cases of eclampsia. More case women than controls were prescribed inhaled corticosteroids before and during pregnancy, and more were taking oral steroids. Case women who took more than 3 doses of a short-acting ␤ 2 agonist per week before pregnancy were at increased risk of pregnancy-induced hypertension, but this level of treatment during pregnancy correlated with a lower risk. Cases more often visited an emergency department for asthma. Using inhaled steroids while pregnant was not associated with the risk of either preeclampsia or pregnancy-induced hypertension. There was no dose-response relationship with inhaled steroids for either of these conditions. Oral steroids were, however, significantly associated with pregnancy-induced hypertension; the adjusted odds ratio was 1.57, and the 95% confidence interval was 1.02-2.41.This study failed to significantly relate the use of inhaled corticosteroids to either pregnancy-induced hypertension or preeclampsia in asthmatic women. These women should be encouraged to continue using inhaled steroids while pregnant to control their asthma. ABSTRACTThere is limited evidence that periodontitis is associated with preterm birth, but why it might induce inflammation and premature termination of pregnancy remains uncertain. The investigators evaluated periodontal status in 36 women at risk of miscarriage or preterm delivery. Amniocentesis was carried out at 15-20 weeks gestation, and a full-mouth periodontal examination was done at approximately the same time. The criterion for periodontitis was at least 1 site with a probing depth of 5 mm or greater in each quadrant. The 2 sites with the deepest pockets were chosen for microbial sampling of intraoral plaque. Vaginal smears also were obtained and cytokine levels estimated in amniotic fluid samples.Chronic periodontitis was diagnosed in 20% of women delivering within the normal period and in 83% of those who had a preterm delivery and an infant with low birth weight. All women with preterm gestations had regularly received dental care. Probing depths differed significantly in the preterm and full-term cases. In no case was the amniotic fluid infec...