Twins prematurity – the influence of prenatal surveillance

Objective: To evaluate the influence of the local prenatal surveillance of twin pregnancies in the obstetrical results.

Methods: A prospective cohort study of multiple pregnancies delivered over a period of 16 years in a tertiary centre was conducted. In this study 861 twin pregnancies were included. They were compared for obstetric complications, gestational age at delivery, mode of delivery and birthweight, according to the place of the surveillance.

Results: Of the 861 cases examined, the following obstetric complications were significantly different: metrorrhagia (p?=?0.039), infections (p?p?=?0.007), PROMPT (p?p?=?0.024). The mode of delivery was similar but occurred mostly ≤32 weeks (p?p?Conclusion: Our results demonstrate the crucial importance of prenatal surveillance be carried in a differentiated referral centers with specific/strict protocols or the urgent implementation of same protocols in all other places of surveillance, since this straight surveillance greatly reduces the occurrence of prenatal complications, mainly PROMPT, PTD.     

The inheritance of corneal endothelial cell density

Background: Although it is known that some corneal diseases and degenerations have a significant heritable background, heritability on corneal endothelial cell density (ECD) has never been clearly determined. Our aim was to determine the heritability of corneal ECD.

Material and methods: Corneal ECD of 114 eyes (66 eyes of 33 monozygotic and 48 eyes of 24 dizygotic pairs; mean age 49.0 ± 15.5 years) was investigated by Konan Noncon Robo NSP-9900 specular microscopy. Structural equation modeling (ACE model) was applied.

Results: Endothelial corneal cell density was highly heritable (82.0%, 95%CI, 70.0–92.0%), whereas the unique environmental contribution was 18.0% (95%CI, 8.0–29.0%). Shared environmental factors had no influence on the endothelial corneal cell density.

Discussion: In this twin study, we established first that the density of the corneal endothelial cells is strongly heritable, which should stimulate future genetic studies to identify genes and pathways that are involved in determining ECD which might in turn lead to future treatments to prevent EC loss.     

Clinical characteristics of migraine in a population-based twin sample: similarities and differences between migraine with and without aura

OBJECTIVE: To look into clinical differences between migraine with and without aura in a population-based sample of migraineurs. BACKGROUND: Migraine presents in two major forms, migraine with and migraine without aura. With the exception of the aura phase, the clinical characteristics of these entities are very similar. Despite this, however, the recent epidemiological data underline differences between migraine with and without aura. We tried to examine whether other features besides the aura differ between these two major forms of migraine. METHODS: We studied 321 twins suffering from migraine with aura and 166 twins with migraine without aura from the population-based Finnish Twin Cohort. Migraine was diagnosed according to the criteria of the International Headache Society (IHS). Analysis was based on the combination of a mailed questionnaire and a telephone interview by a neurologist. Special attention was paid to differences between migraine with and without aura. RESULTS: Some qualities of headaches differed between IHS defined migraine with and without aura. Unilateral headache (Chi-squared p = 0.039) and photophobia (Chi-squared p = 0.010) were more typical for migraine with aura, while nausea was more typical for migraine without aura (Chi-squared p = 0.002). Duration of headache in migraine without aura was also longer than in migraine with aura (Mann-Whitney U-test 0.007). CONCLUSIONS: There are clinical differences between IHS defined migraine with and without aura; even the headache phase between the two entities differs. It is worthwhile distinguishing between them when looking for the elusive genes for these more common forms of migraine.     

Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins

BACKGROUND: Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. AIM: Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. METHODS: Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. RESULTS: Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS: Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition.     

Determinants of bronchial responsiveness to methacholine at school age in twin pairs

The methacholine inhalation challenge test (MIC) was used to evaluate bronchial responsiveness in 67 children who were the products of multiple pregnancies when they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of gestation. None of the children had doctor-diagnosed asthma. The provocative dose of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20) was below 1,000 microg in 10 (15%) children, and they were classified as MIC responders. There were no differences in perinatal or neonatal factors between MIC responders and nonresponders; in particular, MIC responses did not differ between IUGR infants, and children with appropriate growth for gestational age (AGA) at birth. There were seven discordant pairs in which one child was a MIC responder and the other was not; 5 responders were IUGR, and 2 were AGA children (ns). Respiratory tract infections after the neonatal period were equally common in IUGR and AGA children. However, these infections were associated with later bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers of antibiotic courses, episodes of otitis media, and the need for adenoidectomy, tonsillectomy, and tympanostomy were more common in MIC responders than in nonresponders. We conclude that IUGR was not associated with subsequent bronchial hyperresponsiveness in twin pairs assessed by the MIC test. A significant relationship was seen between bronchial hyperresponsiveness and infections after the neonatal period.     

Genetic contribution to individual variation in binocular rivalry rate

Binocular rivalry occurs when conflicting images are presented in corresponding locations of the two eyes. Perception alternates between the images at a rate that is relatively stable within individuals but that varies widely between individuals. The determinants of this variation are unknown. In addition, slow binocular rivalry has been demonstrated in bipolar disorder, a psychiatric condition with high heritability. The present study therefore examined whether there is a genetic contribution to individual variation in binocular rivalry rate. We employed the twin method and studied both monozygotic (MZ) twins (n = 128 pairs) who are genetically identical, and dizygotic (DZ) twins (n = 220 pairs) who share roughly half their genes. MZ and DZ twin correlations for binocular rivalry rate were 0.51 and 0.19, respectively. The best-fitting genetic model showed 52% of the variance in binocular rivalry rate was accounted for by additive genetic factors. In contrast, nonshared environmental influences accounted for 18% of the variance, with the remainder attributed to measurement error. This study therefore demonstrates a substantial genetic contribution to individual variation in binocular rivalry rate. The results support the vigorous pursuit of genetic and molecular studies of binocular rivalry and further characterization of slow binocular rivalry as an endophenotype for bipolar disorder.     

Birth weight is nongenetically associated with glucose intolerance in elderly twins, independent of adult obesity

OBJECTIVES: Using a unique twin approach, we examined the extent to which birth weight is determined by genetic and nongenetic factors and whether associations between birth weight and measures of glucose metabolism are of genetic or nongenetic origin. SETTING/SUBJECTS: An oral glucose tolerance test (OGTT) was performed in a population-based cohort of twins including 138 same-sex monozygotic (MZ) and 214 dizygotic (DZ) twin pairs aged 55-73 years whose birth weight was known. Heritability of birth weight was determined and regression analyses with intra-twin pair differences of birth weight and measures of glucose metabolism, with and without adjustment for adult obesity, were performed. RESULTS: The heritability of birth weight was estimated to be 38%. We demonstrated significant nongenetic associations between birth weight and measures of glucose homeostasis in MZ twins, with a reduction in fasting plasma glucose, 120 min post-OGTT plasma glucose, fasting plasma insulin and HOMA-IR index of 15.7%, 25.5%, 26.4% and 37.2%, respectively, for every 1 kg increase in birth weight. The nongenetic negative associations between birth weight and measures of glucose intolerance were independent of adult obesity, whereas the nongenetic association between birth weight and insulin resistance persisted, although not as strongly, after adjusting for current body size. CONCLUSIONS: We demonstrated a genetic component to birth weight in elderly twins. When adjusting for this influence, we found a nongenetic negative association between birth weight and glucose tolerance as well as insulin resistance that was partially independent of adult obesity. This implies that the foetal environment influences glucose homeostasis in elderly twins.     

Risk factors and adverse maternal and perinatal outcomes for women with dichorionic twin pregnancies complicated by gestational diabetes mellitus: A retrospective cross-sectional study

Aims/IntroductionThe association between gestational diabetes mellitus (GDM) and adverse maternal and perinatal outcomes in twin pregnancies remains unclear. This study was undertaken to highlight risk factors for GDM in women with dichorionic (DC) twins, and to determine the association between GDM DC twins and adverse maternal and perinatal outcomes in a large homogeneous Taiwanese population.Materials and MethodsA retrospective cross‐sectional study was carried out on 645 women with DC twins, excluding pregnancies complicated by one or both fetuses with demise (n = 22) or congenital anomalies (n = 9), who gave birth after 28 complete gestational weeks between 1 January 2001 and 31 December 2018. Univariable and multiple logistic regression analyses were carried out.ResultsMaternal age >34 years (adjusted odds ratio 2.52; 95% confidence interval 1.25–5.07) and pre‐pregnancy body mass index >24.9 kg/m² (adjusted odds ratio 2.83, 95% confidence interval 1.47–5.46) were independent risk factors for GDM in women with DC twins. Newborns from women with GDM DC twins were more likely to be admitted to the neonatal intensive care unit (adjusted odds ratio 1.70, 95% confidence interval 1.06–2.72) than newborns from women with non‐GDM DC twins. Other pregnancy and neonatal outcomes were similar between the two groups.ConclusionsAdvanced maternal age and pre‐pregnancy overweight or obesity are risk factors for GDM in women with DC twins. Except for a nearly twofold increased risk of neonatal intensive care unit admission of newborns, the pregnancy and neonatal outcomes for women with GDM DC twins are similar to those for women with non‐GDM DC twins.     

The complete spectrum of pentalogy of Cantrell in one of a set of dizygotic twins: A case report of a rare congenital anomaly

Rationale:Pentalogy of Cantrell (POC) is an extremely rare syndrome with an estimated incidence of 1:65,000 to 200,000 live births. Its complete form includes a midline epigastric abdominal wall defect, defects affecting the lower sternum, anterior diaphragm, diaphragmatic pericardium, and various intracardiac defects.Patient concerns:We report a case of complete POC affecting only the first-born of a set of premature dizygotic twins.Diagnosis:A giant omphalocele with an eviscerated liver and bowel on prenatal, obstetric ultrasonography at 24 gestational weeks was observed. At birth, physical examination confirmed a massive (10 × 8 cm) epigastric omphalocele in which a significant part of the liver was seen. A postnatal echocardiogram revealed the presence of an ostium secundum atrial septal defect, perimembranous ventricular septal defect, and moderate pulmonary stenosis. X-ray showed an abnormal intrathoracic positioned stomach, which was confirmed with a plain x-ray of the upper intestinal tract with hydrosoluble contrast. Computed tomography (CT) scan revealed the sternum''s absence and a close connection between the pericardial sac and the stomach wall.Interventions:The patient underwent surgical intervention at 18 days of age.Outcomes:Despite adequate and appropriate postoperative treatment, the baby rapidly deteriorated and died 72 hours after surgery.Lessons:POC is a complex, high-mortality syndrome whose management requires a multidisciplinary approach and meticulous planning. Despite all efforts, POC carries a poor prognosis, particularly in patients affected by its complete form.