Volume 42, Issue 2 -

Aim: To perform a systematic review to assess the accuracy of first-trimester ultrasound (US) in the diagnoses of major structural malformations in chromosomally normal fetuses. Methods: References were obtained from the MEDLINE database, without time range limitations. For each, the risk of bias was evaluated and the important data were extracted. Only studies that used first-trimester US to diagnose major structural malformations were included. We evaluated the sensitivity of US over a low-risk unselected population of pregnant women carrying euploid fetuses. Results: A total of 19 studies were included, contributing to 126,937 fetuses and 1399 major malformations. The prevalence of lethal and severe malformations obtained was 1.2% [95% confidence interval (CI), 1.0–1.4]. Both averaged and pooled sensitivity, 50.0% (95% CI 44.1–55.9) and 45.2%, respectively, presented a moderate value for first-trimester US in the detection of structural malformations. Conclusion: Based on our analysis of the data, the average sensitivity of first-trimester US to detect structural malformations was 50%. It is our conviction that US has the potential to evolve in this role by exploiting the natural history of malformations and the development of US techniques.

In 1966, the National Austrian Newborn Screening Program for inherited metabolic and endocrine disorders was initiated. In the last five decades, around four million babies were screened and in more than 2600 babies, various inborn errors of metabolism and endocrine disorders were detected. This health-preventive program was continuously expanded from phenylketonuria and galactosemia to congenital hypothyroidism, biotinidase deficiency, cystic fibrosis, and congenital adrenal hyperplasia. In 2002, the introduction of tandem mass spectrometry substantially increased the number of detectable rare diseases, and now includes disorders of fatty acid oxidation, organic acidurias, and various disorders of amino acid metabolism. In this review, we highlight the development of the Austrian screening program, and pinpoint future disorders and challenges.

Objective: To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation. Methods: One hundred and eighty nine (189) women at 16–24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated. Results: The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (from r=–0.24, P<0.001 to r=–0.03, P=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25 th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25 th centile [endocervical: odds ratio (OR) 0.2; 95% confidence interval (CI), 0.03–0.96; entire cervix: OR 0.17; 95% CI, 0.03–0.9]. Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index, and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD. Conclusion: Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation.

Aims: To explore the association between childhood sexual abuse (CSA), physical abuse, as well as other adverse childhood experiences (ACE), and different obstetrical risk factors/behaviors. Methods: In this cohort study, obstetrical risk factors and perinatal outcome in 85 women exposed to CSA were compared to 170 matched unexposed women. CSA, physical abuse, and ACE were explored by face-to-face interviews and by questionnaire. Data on perinatal outcome were extracted from medical charts. Fisher’s exact, χ 2 -test, and multiple logistic regression were used for statistical analysis. Results: During pregnancy women with CSA experiences were significantly more often smoking (31.7%/9.4%; P<0.0001), had partners abusing drugs (10.6%/1.2%; P<0.0005), experienced physical (16.5%/0; P<0.0001), sexual (12.9%/0; P<0.0001), and emotional abuse (44.7%/1.7%; P<0.0001), reported depression (24.7%/1.8%; P<0.0001), and suicidal ideation (10.6%/0; P<0.0001) than women without CSA experiences. Differences in risk factors were more often correlated with physical than with sexual abuse during childhood. The probability for premature delivery was associated with CSA, physical abuse and ACE as well as with several of the risk factors investigated. Conclusion: Women with CSA, physical, and ACE present with a variety of abuse-associated obstetrical risk factors and an increased risk for premature delivery. Therefore, all types of abusive and other ACE should be considered in prenatal care.

Aims: Peroxisome proliferator-activated receptor-gamma (PPARγ) plays an important role in insulin metabolism, trophoblast differentiation and anti-inflammatory circuits. The aim of this study was to investigate the expression of PPARγ in the placenta of patients with gestational diabetes mellitus (GDM) and the regulation of PPARγ by its agonists in trophoblast tumour cells BeWo in vitro . Methods : PPARγ expression in a total of 80 placentas (40 GDM/40 controls) was analysed by immunohistochemistry using the semi-quantitative immunoreactive score. Furthermore, a quantitative reverse transcription-polymerase chain reaction (PCR) was performed to determine the PPARγ mRNA-expression in both groups. We used a fused and a non-fused BeWo cell culture model for the stimulation with arachidonic acid and 15-Deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ2). Afterwards PPARγ mRNA-expression was analysed by quantitative real-time PCR (RT-PCR) (TaqMan). Results: Using immunohistochemistry we identified a decreased expression of PPARγ in the syncytiotrophoblast and the extravillous trophoblast of GDM placentas compared to normal controls. Furthermore, PPARγ mRNA-expression was reduced in GDM placentas. Stimulation of BeWo cells with arachidonic acid and 15d-PGJ2 caused a downregulation of PPARγ expression. Conclusion: As PPARγ is down regulated by arachidonic acid and 15d-PGJ2, the reduced PPARγ expression in GDM placentas may be due to an altered concentration of fatty acid derivates.

Aim: How long the waiting time may be for the onset of spontaneous labor after prelabor rupture of fetal membranes at term (tPROM) remains controversial. Methods: The study is an observational cohort study of 6032 women. All obstetric patients with no obstetric risk factors, other than tPROM, were included. The analysis focused on the onset of labor (spontaneous vs. induction), maternal morbidity [cesarean section (CS) and chorioamnionitis] and neonatal morbidity (suspected infection) related to a policy of waiting for the onset of spontaneous labor within 48 h of tPROM. Results: tPROM was experienced by 1439 women. A careful clinical management shows a very low rate of clinical chorioamnionitis (2.3%) and neonatal infection rate (2.8%), even after 24 h from tPROM. The overall incidence of CS was 4.5%. Furthermore, a policy of waiting for the onset of spontaneous labor within 48 h of tPROM is associated with a low rate of CS, less than induced labor (OR=1.76; 95% confidence interval 1.03–3.02; P<0.004). Conclusions: Fetal and/or maternal morbidity in tPROM women may not increase if there is a strict analysis of maternal and or fetal risk factors added to a careful clinical management. Moreover, it may be useful to wait for spontaneous labor in order to enhance the patient’s chance of vaginal delivery.

Objective: To compare the effects of oral ferrous bisglycinate 25 mg iron/day vs. ferrous sulfate 50 mg iron/day in the prevention of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women. Design: Randomized, double-blind, intention-to-treat study. Setting: Antenatal care clinic. Sample: 80 healthy ethnic Danish pregnant women. Methods: Women were allocated to ferrous bisglycinate 25 mg elemental iron (Aminojern ® ) (n=40) or ferrous sulfate 50 mg elemental iron (n=40) from 15 to 19 weeks of gestation to delivery. Hematological status (hemoglobin, red blood cell indices) and iron status (plasma iron, plasma transferrin, plasma transferrin saturation, plasma ferritin) were measured at 15–19 weeks (baseline), 27–28 weeks and 36–37 weeks of gestation. Main outcome measures: Occurrence of ID (ferritin <15 μg/L) and IDA (ferritin <12 μg/L and hemoglobin <110 g/L). Results: At inclusion, there were no significant differences between the bisglycinate and sulfate group concerning hematological status and iron status. The frequencies of ID and IDA were low and not significantly different in the two iron groups. The frequency of gastrointestinal complaints was lower in the bisglycinate than in the sulfate group (P=0.001). Newborns weight was slightly higher in the bisglycinate vs. the sulfate group (3601±517 g vs. 3395±426 g, P=0.09). Conclusions: In the prevention of ID and IDA, ferrous bisglycinate was not inferior to ferrous sulfate. Ferrous bisglycinate in a low dose of 25 mg iron/day appears to be adequate to prevent IDA in more than 95% of Danish women during pregnancy and postpartum.

Background : Antenatal magnesium in preterm labor for neuroprotection decreases the incidence of cerebral palsy. However, there are no guidelines on the dose and duration of magnesium infusion for neuroprotection. As increased neonatal serum magnesium concentrations may be related to higher risk of morbidity and mortality, the role of total amount of magnesium and maternal serum magnesium concentrations associated with safe neonatal serum magnesium concentrations is not known. Methods: A retrospective study was conducted on 289 mothers who received antenatal magnesium for neuroprotection as a loading dose of 4–6 g infused over 30 min, followed by a maintenance infusion of 1–2 g/h. Total magnesium dose infused to the mother and maternal serum magnesium concentrations were correlated with neonatal serum magnesium concentrations. Results: Of the 289 mothers, 192 mother/baby dyads had all three measurements (maternal total magnesium dose, and maternal and neonatal serum magnesium concentrations). Magnesium infusion was continued beyond 24 h in 60 mothers. Total maternal magnesium dose at 24 and 48 h of infusion correlated with neonatal serum magnesium concentrations (r=0.55, P<0.0001 and r=0.35, P<0.0001, respectively), but not with maternal serum magnesium concentrations (r=0.004, P=0.98 and r=0.14, P=0.21). However, there was no correlation between the maternal and neonatal serum magnesium concentrations (r=0.10, P=0.15). Conclusion: Total dose of magnesium infused to the mother correlates with neonatal serum magnesium concentrations. To keep neonatal serum magnesium concentrations within a range that is effective for neuroprotection and safe for the neonates, the total dose received by the mother needs to be monitored and limited.

Objective: We sought to compare the efficacy of the double-balloon catheter and dinoprostone for induction of labor among nulliparous women with an unfavorable cervix. Study design: Nulliparous women with a Bishop score <6 were randomized to receive a 10-mg intra-vaginal dinoprostone insert or a double-balloon catheter. Primary outcome was time to delivery. Statistical analyses were performed by intention to treat using the chi-square, Fisher’s exact, and Student’s t -test, as appropriate. Results: The mean induction-to-delivery time was shorter in the double-balloon group as compared to the dinoprostone group (17.9±5.8 vs. 26.3±9.7 h) as was the time from induction to vaginal delivery (19.13±5 vs. 24.45±8.7 h, respectively). More women in the catheter group were delivered within 24 h compared to the dinoprostone group (87.1% vs. 47.4%). Approximately 50% of women in both groups delivered by cesarean section. Conclusion: Induction of labor with the double-balloon catheter in nulliparous women with an unfavorable cervix is associated with a shorter time to delivery compared to dinoprostone.

Study design: The present study is a retrospective review of 500 consecutive births at one academic institution before and after implementation of a uniform thromboprophylaxis policy with heparin for all cesarean deliveries. An “opt-out” policy for ordering physicians was implemented by automatically defaulting to order heparin in the electronic order set used after cesarean delivery. Results: Cesarean delivery rates were similar during both time periods. Heparin thromboprophylaxis was indicated in 99.6% of the cesarean delivery population before implementation and 94.5% after implementation. Prior to implementation only 5.7% received thromboprophylaxis compared to 96.1% after implementation, P<0.0001. Conclusion: An opt-out heparin thromboprophylaxis policy improves compliance with thromboprophylaxis guidelines compared to an opt-in policy. Institutions should consider opt-out heparin thromboprophylaxis policies after cesarean deliveries to improve compliance with recommendations.

Objective: Twin studies offer opportunities to investigate mechanisms underlying sex-associated differences in perinatal outcomes. The objective of the study was to investigate sex-related differences in perinatal complications. Study design: A cohort of 16,045 twin pregnancies – 32,090 twins – was explored for obstetric complications, perinatal and infant mortality, and neonatal morbidities. Results: Twin pregnancies with a female fetus had an increased risk for preeclampsia, but otherwise there were no pregnancy complications associated with fetal sex. After birth, female-female twins had lower early neonatal and infant mortality, and lower risk for respiratory morbidities than male-male twins at all gestational ages. In unlike-sexed twin pairs, very preterm males had higher respiratory morbidity than females and, females were at higher risk for being growth restricted. Conclusion: Male-male twins have higher respiratory morbidity and neonatal mortality than female-female twins. In unliked-sexed twin pairs, the males seem to be protected by having a female co-twin.

Aims: To deduce the origin of preeclampsia characterized by hypertension and proteinuraia on the basis of results from animal studies and its therapeutic strategies. Methods: Sympathetic and parasympathetic zones of female non-pregnant rabbit brain were stimulated electrically with Kurotu’s electrodes. Systolic blood pressure, urine volume, and proteinuria were evaluated before and after the stimulation of autonomic zones. Results: Excitation, hypertension, urine reduction, cloudy urine, and proteinuria were observed following stimulation of the sympathetic zone. A stable state, low blood pressure, increased urine volume, and no proteinuria were observed following stimulation of the parasympathetic zone. Conclusion: Hypertension and proteinuria in preeclampsia are caused by continuous stimulation of the sympathetic nervous center in the hypothalamus through the innervation between the enlarged uterus and hypothalamus in the latter stages of pregnancy or in a complete hydatidiform mole. Future studies are needed to address the potential of pharmacological suppression of an overactive sympathetic nerve system.

Aim: To determine the clinical characteristics and safety of kangaroo mother care (KMC) according to the gestational age (GA) or postmenstrual age (PMA). Methods: We conducted a prospective clinical study in 31 infants between 25 and 32 weeks’ GA. The subjects were categorized into two groups (25–28 weeks’ and 29–32 weeks’ GA groups) to compare the clinical characteristics associated with KMC. Heart rate, respiratory rate, oxygen saturation, blood pressure and body temperature (BT) were longitudinally assessed for 60 min with respect to the PMA group (29–32 weeks’ and 33–36 weeks’ PMA groups). Results: The authors analyzed 70 sessions with 31 infants (25–32 weeks’ GA, birth weight 760–1740 g, 29–36 weeks’ PMA). All infants had statistically significant higher temperatures during KMC than before KMC within clinically acceptable limits (P<0.001). We found a significantly lower variation of BT in the 25–28 weeks’ GA group compared with the 29–32 weeks’ GA group at 33–36 weeks’ PMA, suggesting accelerated skin maturation in more premature infants (P<0.001). Conclusion: Our intermittent KMC was a safe and feasible method for preterm infants. Notably, at the same PMA, preterm infants in the lower at-birth GA group showed an advanced maturation of thermoregulation compared with those in the higher GA group.

Objectives: The aim of this study was to investigate the potential impact of gestational age (GA) estimation on the basis of the last menstrual period (LMP) in comparison with GA based on ultrasound examination on rates of survival and neonatal morbidity among extremely preterm infants. Methods: The Swedish national registry of infants born extremely preterm (Extremely Preterm Infants in Sweden Study), including infants born before 27 weeks of gestation, was used to identify 645 infants with available information. Incidences of stillbirth, survival, small for GA (SGA), and major neonatal morbidity were calculated in relationship to the GA estimated by each of the approaches. Results: Pregnancies, in general, appeared to be longer when GA was estimated by LMP than by ultrasound (17.2% of the pregnancies were longer than 27 weeks). The incidences of stillbirth, neonatal death, and major neonatal morbidity in relationship to GA were similar for both groups. The risks for SGA were elevated when GA according to ultrasound examination was at least 7 days shorter than GA based on the LMP. Conclusions: In our cohort of infants born extremely preterm, estimation of GA on the basis of LMP indicated a longer pregnancy than estimated by ultrasound but did not influence the incidences of neonatal survival and morbidity.

Objective: To determine the reference values of nuchal translucency (NT) thickness at 11–14 weeks of gestation in a sample of the Brazilian population. Methods: A retrospective cross-sectional study was carried out with singleton gestations and fetuses with a crown-rump length (CRL) of 45–84 mm. NT thickness was performed according to the guidelines of the Fetal Medicine Foundation (FMF), London, UK. To evaluate the correlation between NT thickness and gestational age (GA), polynomial equations were calculated, with determination coefficient (R 2 ) adjustments, as proposed by Altman-Chitty. Results: A total of 1420 pregnancies were assessed. The mean of the gestational age was 12.69±0.78 weeks. The mean maternal age was 28.78±6.81 years. The mean NT thickness (mm) for the CRL intervals of 45├50; 50├55; 55├60; 60├65; 65├70; 70├75; 75├80; 80├85 was 1.30±0.74; 1.34±0.60; 1.48±0.48; 1.56±0.68; 1.71±0.67; 1.78±0.69; 1.67±0.43; 1.67±0.58; respectively. The following second-order equation best represented the correlation between NT thickness and GA: NT=–1.2570+0.0765×GA–0.0005×GA 2 (R 2 =0.05). Conclusion: The reference values for NT thickness were determined for a sample of the Brazilian population. Further studies are required to evaluate the real need for including these values in first-trimester screening for chromosomal defects in Brazil.