Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next‐generation ...sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in‐house‐designed kidney‐gene panel. In families where candidate variants were not identified, whole‐exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney‐gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses—presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney‐gene panel and additional variants were identified. Next‐generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT‐ROBO signaling is implicated in human bilateral kidney agenesis.
The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%–6% of birth cohorts in the Nordic countries. The risk of ...placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown.
To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries.
In a population-based cohort study, with data from national health registries in Denmark (1994–2014), Finland (1990–2014), Norway (1988–2015) and Sweden (1988–2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation.
The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35–2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61–0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were –0.16 percentage points (95% confidence interval, –0.19 to –0.12) and –0.06 percentage points (95% confidence interval, –0.06 to –0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14–0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16–0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies.
The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology.
Objective
Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac ...malformations.
Design
Register‐based study.
Setting
Denmark.
Population
364 012 singleton pregnancies from 2007 to 2014.
Methods
We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions.
Main outcome measures
Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1 year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated.
Results
SCM were reported in 972 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval CI 0.89–5.13), 1.73 (95% CI 1.08–2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 95% CI 6.41–47.2), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52–2.30) and 1.38 (95% CI 1.00–1.92) for SCM and other cardiac malformations, respectively.
Conclusions
Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered.
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Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.
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Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.
The nonparametric estimator of the Extended Facet reference technology for the Constant Returns to Scale case has attracted some attention, because the associated production frontier by construction ...does only include strongly efficient faces of maximal dimension, or strongly efficient faces that are part of such strongly efficient faces of maximal dimension. The strongly efficient faces of maximal dimension are denoted Full Dimensional Efficient Facets (FDEFs). The identification of such strongly efficient facets is facilitated by removing all inefficient and all strongly efficient but not extreme efficient DMUs from the estimation procedure of the technology set. Any face that i) is passing through the origin and with (
s
+
m
− 1) linear independent extreme efficient observed DMUs positioned on it and ii) with a normal vector with strict positive (strict negative) output (input) components, is a FDEF, where
s
(
m
) is the number of outputs (inputs). It is, however, not correct that every face that satisfies only i) is a FDEF. We denote a face (a subface) that satisfies only condition i) but not condition ii) for an
AP-face (an AP-subface)
. It is proved that a radial projection of any output input combination in the estimated EXFA technology set is positioned on the strongly efficient frontier if and only if i) no
A
P
-(sub)faces exist, ii) a regulaty condition RC1 is satisfied and only dual multiplier constraints corresponding to extreme efficient DMUs are included in the estimation. A test for the fulfillment of the condition that no
A
P
-(sub)faces exist is provided.
We present detailed neutron scattering studies of the static and dynamic stripes in an optimally doped high-temperature superconductor, La_{2}CuO_{4+y}. We observe that the dynamic stripes do not ...disperse towards the static stripes in the limit of vanishing energy transfer. Therefore, the dynamic stripes observed in neutron scattering experiments are not the Goldstone modes associated with the broken symmetry of the simultaneously observed static stripes, and the signals originate from different domains in the sample. These observations support real-space electronic phase separation in the crystal, where the static stripes in one phase are pinned versions of the dynamic stripes in the other, having slightly different periods. Our results explain earlier observations of unusual dispersions in underdoped La_{2-x}Sr_{x}CuO_{4} (x=0.07) and La_{2-x}Ba_{x}CuO_{4} (x=0.095).
Here we show how encapsulation of a squaraine dye in a rotaxane structure renders the dye that normally start decomposing at 100 °C stable above 250 °C. This thermal stabilisation makes new ...applications possible, and we demonstrate how the squaraine rotaxane can mediate laser welding of polyethylene, a process that requires thermal stability.
Encapsulation of a squaraine dye in a rotaxane structure renders the dye that normally start decomposing at 100 °C stable above 250 °C. This thermal stabilisation makes new applications possible, and we demonstrate how the squaraine rotaxane can mediate laser welding of polyethylene.
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