Management of suspected primary Toxoplasma gondii infection in pregnant women in Norway: twenty years of experience of amniocentesis in a low-prevalence population.

BACKGROUND: Primary infection with Toxoplasma gondii during pregnancy may pose a threat to the fetus. Women infected prior to conception are unlikely to transmit the parasite to the fetus. If maternal serology indicates a possible primary infection, amniocentesis for toxoplasma PCR analysis is performed and antiparasitic treatment given. However, discriminating between primary and latent infection is challenging and unnecessary amniocenteses may occur. Procedure-related fetal loss after amniocentesis is of concern. The aim of the present study was to determine whether amniocentesis is performed on the correct patients and whether the procedure is safe for this indication. METHODS: Retrospective study analysing data from all singleton pregnancies (n = 346) at Oslo University Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma infection during 1993-2013. Maternal, neonatal and infant data were obtained from clinical hospital records, laboratory records and pregnancy charts. All serum samples were analysed at the Norwegian Institute of Public Health or at the Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses were performed at Oslo University Hospital by experienced personnel. Time of maternal infection was evaluated retrospectively based on serology results. RESULTS: 50% (173) of the women were infected before pregnancy, 23% (80) possibly in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring were infected with toxoplasma, one of them with negative PCR in the amniotic fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs) (Q1 = 15, Q3 = 22), with median sample volume 4 ml (Q1 = 3, Q3 = 7). Two miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One of these had severe fetal toxoplasma infection. CONCLUSIONS: Half of our study population were infected before pregnancy. In order to reduce the unnecessary amniocenteses we advise confirmatory serology 3 weeks after a suspect result and suggest that the serology is interpreted by dedicated multidisciplinary staff. Amniocentesis is safe and useful as a diagnostic procedure in diagnosing congenital toxoplasma infection when performed after 15 GW.

Paternal psychological response after ultrasonographic detection of structural fetal anomalies with a comparison to maternal response: a cohort study.

BACKGROUND: In Norway almost all pregnant women attend one routine ultrasound examination. Detection of fetal structural anomalies triggers psychological stress responses in the women affected. Despite the frequent use of ultrasound examination in pregnancy, little attention has been devoted to the psychological response of the expectant father following the detection of fetal anomalies. This is important for later fatherhood and the psychological interaction within the couple. We aimed to describe paternal psychological responses shortly after detection of structural fetal anomalies by ultrasonography, and to compare paternal and maternal responses within the same couple. METHODS: A prospective observational study was performed at a tertiary referral centre for fetal medicine. Pregnant women with a structural fetal anomaly detected by ultrasound and their partners (study group,n=155) and 100 with normal ultrasound findings (comparison group) were included shortly after sonographic examination (inclusion period: May 2006-February 2009). Gestational age was >12 weeks. We used psychometric questionnaires to assess self-reported social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression): Impact of Event Scale. General Health Questionnaire and Edinburgh Postnatal Depression Scale. Fetal anomalies were classified according to severity and diagnostic or prognostic ambiguity at the time of assessment. RESULTS: Median (range) gestational age at inclusion in the study and comparison group was 19 (12-38) and 19 (13-22) weeks, respectively. Men and women in the study group had significantly higher levels of psychological distress than men and women in the comparison group on all psychometric endpoints. The lowest level of distress in the study group was associated with the least severe anomalies with no diagnostic or prognostic ambiguity (p < 0.033). Men had lower scores than women on all psychometric outcome variables. The correlation in distress scores between men and women was high in the fetal anomaly group (p < 0.001), but non-significant in the comparison group. CONCLUSION: Severity of the anomaly including ambiguity significantly influenced paternal response. Men reported lower scores on all psychometric outcomes than women. This knowledge may facilitate support for both expectant parents to reduce strain within the family after detectionof a fetal anomaly.

The relation of psychological distress to salivary and serum cortisol levels in pregnant women shortly after the diagnosis of a structural fetal anomaly.

OBJECTIVE: To examine the association between psychological distress and levels of salivary cortisol (SalC) and the ratio of serum cortisol to cortisol-binding globulin (SC/CBG) in pregnant women shortly after the diagnosis of a structural fetal anomaly. DESIGN. A prospective, observational study. SETTING: Tertiary referral center for fetal medicine. POPULATION: Pregnant women with (study group, n=126) and without a fetal structural anomaly (comparison group, n=106) were included. Gestational age (GA) was >12weeks. METHODS: Psychological distress was assessed by Impact of Event Scale (IES-22), General Health Questionnaire (GHQ-28) and Edinburgh Postnatal Depression Scale (EPDS). Salivary cortisol was measured in the evening and SC/CBG in the morning. MAIN OUTCOME MEASURES. Levels of SalC (in nanomoles per liter) and SC/CBG. RESULTS: Median (range) GA at assessment was 19 (12-38) and 19 (13-22)weeks in the study and the comparison group, respectively. The study group had significantly higher psychological distress levels (p≤0.001) than the comparison group in all outcome measures. Salivary cortisol correlated with GA in both groups (p<0.004). In subanalyses including only women with GA 18-22 weeks, and excluding smokers or women with chronic diseases or medication which might interfere with cortisol levels, there were no relations of SalC or SC/CBG with the psychometric variables in the study group. CONCLUSIONS. Women with detected fetal malformation had high psychological distress scores. The lack of association between psychological distress and SalC or SC/CBG suggests a blunted response of the hypothalamic-pituitary-adrenal axis following recent psychological stress activation in the second trimester of pregnancy.

Maternal psychological responses during pregnancy after ultrasonographic detection of structural fetal anomalies: A prospective longitudinal observational study.

In this longitudinal prospective observational study performed at a tertiary perinatal referral centre, we aimed to assess maternal distress in pregnancy in women with ultrasound findings of fetal anomaly and compare this with distress in pregnant women with normal ultrasound findings. Pregnant women with a structural fetal anomaly (n = 48) and normal ultrasound (n = 105) were included. We administered self-report questionnaires (General Health Questionnaire-28, Impact of Event Scale-22 [IES], and Edinburgh Postnatal Depression Scale) a few days following ultrasound detection of a fetal anomaly or a normal ultrasound (T1), 3 weeks post-ultrasound (T2), and at 30 (T3) and 36 weeks gestation (T4). Social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression) were the main outcome measures. The median gestational age at T1 was 20 and 19 weeks in the group with and without fetal anomaly, respectively. In the fetal anomaly group, all psychological distress scores were highest at T1. In the group with a normal scan, distress scores were stable throughout pregnancy. At all assessments, the fetal anomaly group scored significantly higher (especially on depression-related questions) compared to the normal scan group, except on the IES Intrusion and Arousal subscales at T4, although with large individual differences. In conclusion, women with a known fetal anomaly initially had high stress scores, which gradually decreased, resembling those in women with a normal pregnancy. Psychological stress levels were stable and low during the latter half of gestation in women with a normal pregnancy.

Umbilical artery Doppler flow velocity waveforms after transplacental amniocentesis.

OBJECTIVE: To assess the influence of transplacental versus nontransplacental needle passage during genetic amniocentesis on umbilical artery (UA) pulsatility index (PI) and fetal heart rate (FHR). METHODS: Genetic amniocentesis was performed in 205 women with no major fetal malformations detected by prenatal ultrasound at a median gestational age of 14 weeks and 3 days (range 13 weeks and 1 day to 18 weeks and 6 days). Chromosomal abnormalities were observed in five fetuses. These pregnancies were excluded from further analyses. The study group consisted of 56 of the remaining 200 women in whom amniocentesis had been performed transplacentally. As controls two patients with nontransplacental needle passage were chosen for each woman in the study group, matched for gestational age (+/- 3 days) and as far as possible for the indication for amniocentesis. The UA PI and the FHR were measured immediately before and after the amniocentesis. RESULTS: Amniocentesis did not cause significant changes in UA PI and FHR within or between the two groups. Division of the study population into three subgroups dependent on gestational age did not alter the results. Pregnancy outcome was similar in the two groups. CONCLUSION: Transplacental needle passage during amniocentesis did not induce any changes in UA PI or FHR relative to a group with nontransplacental amniocentesis.

Antenatal maternal emotional distress and duration of pregnancy.

OBJECTIVE(S): We sought to prospectively study the association between antenatal emotional distress and gestational length at birth as well as preterm birth. STUDY DESIGN: We followed up 40,077 primiparous women in the Norwegian Mother and Child Cohort Study. Emotional distress was reported in a short form of the Hopkins Symptom Checklist-25 (SCL-5) at 17 and 30 weeks of gestation. Gestational length at birth, obtained from the Medical Birth Registry of Norway, was used as continuous (gestational length in days) and categorized (early preterm (22-31 weeks) and late preterm (32-36 weeks) versus term birth (≥ 37 weeks)) outcome, using linear and logistic regression analysis, respectively. Births were divided into spontaneous and provider-initiated. RESULTS: Of all women, 7.4% reported emotional distress at 17 weeks, 6.0% at 30 weeks and 5.1% had a preterm birth. All measurements of emotional distress at 30 weeks were significantly associated with a reduction of gestational length, in days, for provider-initiated births at term. Emotional distress at 30 weeks showed a reduced duration of pregnancy at birth of 2.40 days for provider-initiated births at term. An increase in emotional distress from 17 to 30 weeks was associated with a reduction of gestational length at birth of 2.13 days for provider-initiated births at term. Sustained high emotional distress was associated with a reduction of gestational length at birth of 2.82 days for provider-initiated births. Emotional distress did not increase the risk of either early or late preterm birth. CONCLUSION: Emotional distress at 30 weeks, an increase in emotional distress from 17 to 30 weeks and sustained high levels of emotional distress were associated with a reduction in gestational length in days for provider-initiated term birth. We found no significant association between emotional distress and the risk of preterm birth.

Maternal psychological distress and placental circulation in pregnancies after a previous offspring with congenital malformation.

INTRODUCTION: Antenatal maternal psychological distress may be associated with reduced placental circulation, which could lead to lower birthweight. Studies investigating this in humans show mixed results, which may be partially due to type, strength and timing of distress. In addition, the arterial vascular resistance measures often used as outcome measures do not detect smaller changes in placental volume blood flow. We aimed to investigate the effect of a specific stressor, with increased levels of stress early in pregnancy, on the fetoplacental volume blood flow in third trimester. METHODS: This was a prospective observational study of 74 pregnant women with a congenital malformation in a previous fetus or child. Psychological distress was assessed twice, around 16 and 30 weeks' gestation. Psychometric measures were the General Health Questionnaire-28 (subscales anxiety and depression), Edinburgh Postnatal Depression Scale, and Impact of Event Scale-22 (subscales intrusion, avoidance, and arousal). Placental circulation was examined at 30 weeks, using Doppler ultrasonography, primarily as fetoplacental volume blood flow in the umbilical vein, normalized for abdominal circumference; secondarily as vascular resistance measures, obtained from the umbilical and the uterine arteries. RESULTS: Maternal distress in second but not third trimester was associated with increased normalized fetoplacental blood flow (P-values 0.006 and 0.013 for score > mean for depression and intrusion, respectively). Post-hoc explorations suggested that a reduced birthweight/placental weight ratio may mediate this association. Psychological distress did not affect vascular resistance measures in the umbilical and uterine arteries, regardless of adjustment for confounders. CONCLUSIONS: In pregnant women with a previous fetus or child with a congenital malformation, higher distress levels in second trimester were associated with third trimester fetoplacental blood flow that was higher than expected for the size of the fetus. The results do not support placental blood flow reduction as a pathway between maternal distress and reduced birthweight.

Does antenatal maternal psychological distress affect placental circulation in the third trimester?

INTRODUCTION: Some types of antenatal maternal psychological distress may be associated with reduced fetal growth and birthweight. A stress-mediated reduction in placental blood flow has been suggested as a mechanism. Previous studies have examined this using ultrasound-derived arterial resistance measures in the uterine (UtA) and umbilical (UA) arteries, with mixed conclusions. However, a reduction in placental volume blood flow may occur before changes in arterial resistance measures are seen. Fetoplacental volume blood flow can be quantified non-invasively in the umbilical vein (UV). Our objective was to study whether specific types of maternal psychological distress affect the placental circulation, using volume blood flow quantification in addition to arterial resistance measures. METHODS: This was a prospective observational study of 104 non-smoking pregnant women (gestational age 30 weeks) with uncomplicated obstetric histories. Psychological distress was measured by General Health Questionnaire-28 (subscales anxiety and depression) and Impact of Event Scale-22 (subscales intrusion, avoidance and arousal). UtA and UA resistance measures and UV volume blood flow normalized for fetal abdominal circumference, were obtained by Doppler ultrasound. RESULTS: IES intrusion scores above the mean were associated with a reduction in normalized UV volume blood flow (corresponding to -0.61 SD; P = 0.003). Adjusting for UA resistance increased the strength of this association (difference -0.66 SD; P<0.001). Other distress types were not associated with UV volume blood flow. Maternal distress was not associated with arterial resistance measures, despite adjustment for confounders. CONCLUSIONS: Intrusive thoughts and emotional distress regarding the fetus were associated with reduced fetoplacental volume blood flow in third trimester. Uterine and umbilical artery resistance measures were not associated with maternal distress. Our findings support a decrease in fetoplacental blood flow as a possible pathway between maternal distress and reduced fetal growth.