Association of amnioinfusion volume at the time of surgery for twin-twin transfusion syndrome and latency to delivery

Objective

To evaluate the impact of amnioinfusion and other peri-operative factors on pregnancy outcomes in the setting of Twin-twin transfusion syndrome (TTTS) treated via fetoscopic laser photocoagulation (FLP).

Methods

Retrospective study of TTTS treated via FLP from 2010 to 2019. Pregnancies were grouped by amnioinfusion volume during FLP (<1 L vs. ≥1 L). The primary outcome was latency from surgery to delivery. An amnioinfusion statistic (AIstat) was created for each surgery based on the volume of fluid infused and removed and the preoperative deepest vertical pocket. Regression analysis was planned to assess the association of AIstat with latency.

Results

Patients with amnioinfusion of ≥1 L at the time of FLP had decreased latency from surgery to delivery (61 ± 29.4 vs. 73 ± 28.8 days with amnioinfusion <1 L, p < 0.001) and increased preterm prelabor rupture of membranes (PPROM) <34 weeks (44.7% vs. 33.5%, p = 0.042). Amnioinfusion ≥1 L was associated with an increased risk of delivery <32 weeks (aRR 2.6, 95% CI 1.5–4.5), 30 weeks (aRR 2.4, 95% CI 1.5–3.8), and 28 weeks (aRR 1.9, 95% CI 1.1–2.3). Cox-proportional regression revealed that AIstat was inversely associated with latency (HR 1.1, 95% CI 1.1–1.2).

Conclusion

Amnioinfusion ≥1 L during FLP was associated with decreased latency after surgery and increased PPROM <34 weeks.     

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: −1.167; 95% credible interval [CrI]: −2.01, −0.33; p = 0.021; I²: 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I²: 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: −0.43, 1.49; p = 0.131; I²: 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.     

Chromosomal and subchromosomal anomalies associated to small for gestational age fetuses with no additional structural anomalies

Objectives: To assess the chromosomal and subchromosomal anomalies in small for gestational age (SGA) fetuses with no additional structural anomalies and their clinical outcomes. Methods: This study retrospectively reviewed the 128 SGA fetuses with no additional anomalies and underwent genetic testing with karyotyping and chromosomal microarray analysis (CMA). Stratified analysis was performed according to the existence of maternal risk factors for SGA (yes or no), gestational age at onset (before or after 32 weeks), presence of oligohydraminos (yes or no), and umbilical artery Doppler flow (normal or abnormal). Results: Chromosomal anomalies were identified in 6 (4.7%) SGA fetuses and pathogenic subchromosomal anomalies in 4 (3.1%) by microarray analysis. Chromosomal and subchromosomal anomalies were more frequently observed in cases with oligohydraminos (P = .017) and with early-onset SGA (P = .042). No differences were observed in relation to the existence of maternal risk factors and abnormal umbilical artery Doppler flow. Overall survival rate was 75.0% with different rates in the early and the late onset group (P < .001). Conclusions: There is a 3.3% incremental yield of subchromosomal anomalies in CMA above karyotyping in SGA fetuses. Chromosomal microarray analysis is recommended in SGA fetuses with no additional structural anomalies, especially coexisting with oligohydraminos and being early onset.     

Obstetrical outcomes following amniocentesis performed after 24 weeks of gestation: A systematic review and meta-analysis

To evaluate obstetrical outcomes for women having late amniocentesis (on or after 24 weeks). Electronic databases were searched from inception to January 1st, 2023. The obstetrical outcomes evaluated were gestational age at delivery, preterm birth (PTB) < 37 weeks, PTB within 1 week from amniocentesis, premature prelabor rupture of membranes (pPROM), chorionamnionitis, placental abruption, intrauterine fetal demise (IUFD) and termination of pregnancy (TOP). The incidence of PTB <37 weeks was 4.85% (95% CI 3.48–6.56), while the incidence of PTB within 1 week was 1.42% (95% CI 0.66–2.45). The rate of pPROM was 2.85% (95% CI 1.21–3.32). The incidence of placental abruption was 0.91% (95% CI 0.16–2.25), while the rate of IUFD was 3.66% (95% CI 0.00–14.04). The rate of women who underwent TOP was 6.37% (95%CI 1.05–15.72). When comparing amniocentesis performed before or after 32 weeks, the incidence of PTB within 1 week was 1.48% (95% CI 0.42–3.19) and 2.38% (95% CI 0.40–5.95). Amniocentesis performed late after 24 weeks of gestation is an acceptable option for patients needing prenatal diagnosis in later gestation.     

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age

Objective

To investigate whether perioperative fetal hemodynamic changes in twin-to-twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years.

Methods

Doppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008-2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley-III cognitive/motor developmental test-score > 2SD below the mean.

Results

Long-term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17-21.05, P = .03), a change from normal umbilical artery pulsatility index (UA-PI) presurgery to UA-PI >p95 postsurgery (OR 4.19; 95% CI: 1.04-16.87, P = .04), a change from normal to MCA-PSV >1.5MoM (OR 4.75; 95% CI: 1.43-15.77, P = .01).

Conclusion

Perioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.     

Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37–38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89–1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36–2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.     

Twin-twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene-environment interaction?

We report a case of a twin-twin transfusion syndrome (TTTS) recipient who, after successful fetoscopic surgery, developed a large pericardial effusion and calcifications of the aorta and main pulmonary artery. The donor fetus never had cardiac strain and never developed cardiac calcifications. A heterozygous likely pathogenic variant in ABCC6 (c.2018T > C, p.Leu673Pro) was identified in the recipient twin. While TTTS recipient twins are at risk of arterial calcifications and right heart failure secondary to the disease, calcifications of the great vessels are also observed in generalized arterial calcification of infancy, a Mendelian genetic disorder with associated biallelic pathogenic variations in ABCC6 or ENPP1, which can result in significant pediatric morbidity or mortality. The recipient twin in this case had some degree of cardiac strain prior to TTTS surgery; however, the progressive calcification of the aorta and pulmonary trunk occurred weeks after TTTS resolution. This case raises the possibility of a gene-environment interaction and emphasizes the need for genetic evaluation in the setting of TTTS and calcifications.     

Transcervical (TC) and transabdominal (TA) CVS for prenatal diagnosis in rotterdam: Experience with 3611 cases

Data from 3611 consecutive CVS (TC, N= 1780; TA, N= 1831) were analysed with emphasis put on influence of maternal and gestational age at CVS on the fetal loss rate < 28 weeks. For TC-CVS the gestational age varied from 9.3–11.6 weeks, for TA-CVS from 9.3–20 weeks. Sampling efficacy at first attempt was 86.5 per cent and 95 per cent respectively. In 4.6 per cent an abnormal result was established. In older mothers (N=2362) the fetal loss rate was significantly higher (p = <0.05) when sampled before 12 weeks (TC-CVS 6.2 per cent, TA-CVS 5.8 per cent). When the CVS (TA) was performed after 12 weeks the fetal loss rate decreased to 2.4 per cent. In 1079 younger women the fetal loss rate remained low (TC 2.8 per cent; TA < 12 weeks 1.8 per cent; TA > 12 weeks 1.7 per cent) and was not influenced by gestational age at the time of sampling. We concluded both methods safe and reliable when the choice of application considers maternal age.     

Blood transferrin receptor expression in chromosomally abnormal fetuses

In a cross-sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17–32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean=79·8 per cent, range=60–98 per cent) and nucleated red cell count (mean=10·4 × 10⁹ per 1, range=1·0–25·0 × 10⁹ per 1) were significantly higher than the appropriate normal mean for gestation (z=3·92, P<0·0001 and z=3·69, P<0·001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression.     

Specific dynamic action affects the hydrostatic pressure tolerance of the shallow-water spider crab <Emphasis Type="Italic">Maja brachydactyla</Emphasis>

The bathymetric distribution of marine benthic invertebrates is likely governed by a combination of ecological and physiological factors. The present study investigates oxygen consumption and heartbeat rate in response to attempted feeding at 1, 100 and 150 atm in the shallow-water spider crab, Maja brachydactyla, from temperate European waters. No significant difference was evident between the resting heartbeat rate of specimens at 1 or 100 atm, which were 56 and 65 bpm, respectively (Mann–Whitney, U = 5382.0; n = 95, 98; p = 0.079). However, at 150 atm the resting heartbeat rate was significantly higher than that observed for 100 atm at 108 bpm (Mann–Whitney, U = 149.0; n = 45, 98; p < 0.001). At 150 atm, feeding was never observed and coupled with the elevated resting heartbeat rate; it is suggested by 150 atm continued survival is unfeasible. At 1 and 100 atm, feeding instigated a distinct increase in heartbeat rate, which remained elevated for over 30 h. This increase peaked within 1 h at 1 atm. At 100 atm, this required 4 h and postprandial oxygen consumption was significantly higher than at 1 atm (Kruskal–Wallis, H = 85.036; df = 2; p < 0.001). Elevated hydrostatic pressure is hypothesized to extend the duration and the total metabolic energy devoted to specific dynamic action. The metabolic requirements of feeding under hyperbaric conditions may even reach such a critical demand that feeding is entirely inhibited.     

Abnormal immunological development in fetuses with trisomy 18

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20–36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T- and natural killer (NK) cell counts were significantly lower (t= − 7·63, P<0·001 and t= − 3·58, P<0·01, respectively); the mean B-cell count was not significantly different (t= − 1·32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.     

Maternal serum alfa-fetoprotein levels in the pregnancy complicated by hypertension

Maternal serum alpha-fetoprotein (MSAFP) was determined in patients 33 to 40 weeks pregnant, and the results were analysed with consideration of the presence and quality of hypertensive disease that complicated many of the pregnancies. Patients with incompletely controlled hypertension had significantly higher MSAFP levels than control patients with pregnancies uncomplicated by any risk factor. MSAFP elevation was greatest in pre-eclampsia (301·6 ± 147·6 kU/L, n = 35) > chronic hypertension with superimposed pre-eclampsia (240·4±74.7 kU/L, n = 30) > chronic hypertension (204·1± 105·3 kU/L, n=141). Each was significantly increased (P< 0·0001) over control pregnant patients' levels (104·3 ± 38·8, n= 187). At each gestational week from 33 weeks to term, MSAFP of combined hypertensive women was significantly greater than corresponding control levels (P< 0·003 to < 0·000l). The magnitude and time of onset of MSAFP increase may indicate severe fetal distress.     

Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options

The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001). We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made. Copyright © 2008 John Wiley & Sons, Ltd.     

Thermal Inactivation of Human Norovirus Surrogates

We investigated the thermal inactivation profiles of murine norovirus (MNV), Hepatitis A virus (HAV), and feline calicivirus (FCV), which are surrogates for the study of human noroviruses. Thermal inactivation of MNV and FCV were evaluated at 37, 50, and 60°C and HAV at 37, 50, 60, and 70°C. All viral surrogates were relatively stable at 37°C. MNV and FCV decimal reduction times (D-values) at 50°C were statistically significantly different (P < 0.05) with MNV being more stable. Both surrogates had comparable, low D-values at 60°C. HAV had significantly higher (P < 0.05) D-values than both MNV and FCV at 50 and 60°C. Overall, the infectivity assay results indicate that HAV is resistant to thermal inactivation while MNV is moderately resistant and FCV is least resistant.     

A cross-country comparison of pregnant women's decision-making and perspectives when opting for non-invasive prenatal testing in the Netherlands and Belgium

Background

The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries.

Methods

A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination.

Results

Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p < 0.001), intention to terminate the pregnancy in case of confirmed trisomy 21 (NL: 51% vs. BE: 62%, p = 0.003) and trisomy 13/18 (NL: 80% vs. BE: 73%, p = 0.020). More Belgian women considered trisomy 21 a severe condition (NL: 64% vs. BE: 81%, p < 0.001). Belgian women more frequently indicated that they believed parents are judged for having a child with trisomy 21 (BE: 42% vs. NL: 16%, p < 0.001) and were less positive about quality of care and support for children with trisomy 21 (BE: 23% vs. NL: 62%, p < 0.001).

Conclusion

Differences in women's decision-making regarding NIPT and the conditions screened for may be influenced by counseling aspects and country-specific societal and cultural contexts.     

The impact of non-invasive prenatal testing on anxiety in women considered at high or low risk for aneuploidy after combined first trimester screening

Objective: The aim of this study was to (1) examine the psychological impact of non-invasive prenatal testing (NIPT) in women with a high-risk (≥1 : 300) and low-risk (≤1 : 301) result on combined first trimester screening (cFTS) and (2) to examine factors influencing anxiety and decision-making in both risk populations. Method: Questionnaires and structured interviews were administered to low (n = 50) and high (n = 63) risk women at the time of NIPT blood draw (point A) and again at least 1 week after receiving their NIPT result (point B). Anxiety levels were measured at these two time points using the State–Trait Anxiety Inventory. Results: Both high-risk and low-risk cFTS groups demonstrated similar intrinsic (trait) anxiety levels (36 ± 10 vs 35 ± 10; p = 0.70). High-risk women had significantly higher levels of state anxiety at point A than low-risk women (42 ± 11 vs 36 ± 11; p < 0.01). Both groups had a statistically significant reduction (p < 0.01), to similar final levels of state anxiety at point B (30 ± 11 vs 29 ± 8; p = 0.61). Conclusion: Women receiving a high-risk result on cFTS have higher levels of state anxiety than their low-risk counterparts. Following a low-risk NIPT result, the anxiety levels in both populations are reduced to similar levels. © 2017 John Wiley & Sons, Ltd.