Frank P. Schubert

Association between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus

OBJECTIVE To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM). METHODS In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models. RESULTS Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM. CONCLUSION There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.

Two is better than one: A case of homozygous myotonic dystrophy type 1

Myotonic dystrophy type 1 is an autosomal dominant condition caused by a trinucleotide CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase gene. The phenotypic features of myopathic facies, generalized weakness, and myotonia are thought to be dependent on repeat number, with larger expansions generally leading to earlier and/or more severe disease. The vast majority of individuals are heterozygous for an expanded allele and an allele in the normal range. In this clinical report, we describe two brothers with congenital myotonic dystrophy type 1. The younger of the two siblings is one of only 13 homozygous patients ever reported in the literature. He carries two expanded alleles: one with 1,170 repeats and the other with >100 repeats. We present his clinical picture in relation to his more severely affected heterozygous brother as well as other published homozygous cases. Finally, we discuss the inconsistency between repeat size and symptomatic expression as it applies to the current proposed mechanisms of myotonic dystrophy type 1 pathogenicity.

Predictors of sleep-disordered breathing in pregnancy:

BACKGROUND Sleep‐disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES The objective of this study was to develop predictive models of sleep‐disordered breathing during pregnancy. STUDY DESIGN Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self‐reported snoring ≥3 days per week. Participants underwent in‐home portable sleep studies for sleep‐disordered breathing assessment in early (6–15 weeks gestation) and mid pregnancy (22–31 weeks gestation). Sleep‐disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep‐disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver‐operating‐characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep‐disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep‐disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep‐disordered breathing in early pregnancy, sleep‐disordered breathing in mid pregnancy, and new onset sleep‐disordered breathing in mid pregnancy with 10‐fold cross‐validated area under the receiver‐operating‐characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep‐disordered breathing. These results can help with screening for sleep‐disordered breathing in the clinical setting and for future clinical treatment trials.

Pseudomonoamniotic Pregnancy: Case Report and Review of Etiologic Considerations

Pseudomonoamniotic gestations are increasingly recognized through sonographic surveillance of monochorionic twins, though etiologic factors remain undefined. We present a case of spontaneous pseudomonoamniotic twins and propose umbilical cord insertion proximity as a sonographic marker. Systematic review of the literature was performed and additional cases with similar findings were noted. Approximately 75% of reported cases (28/37) were deemed spontaneous and several included short inter-cord distances. Shunting of blood away from the membranes in the region between the cord insertions may be responsible for membrane rupture. Further investigation is needed into short inter-cord distance as a marker for monochorionic twins at risk to become a pseudomonoamniotic gestation.

Complications and Outcomes of Pregnancy and Cesarean Delivery in Women With Neuropathic Bladder and Lower Urinary Tract Reconstruction

OBJECTIVE To determine the outcomes of pregnancy and cesarean delivery (CD) in women with neuropathic bladder (NB) and pediatric lower urinary tract reconstruction (LUTR) as these women often have normal fertility and may become pregnant. METHODS We reviewed consecutive patients with NB due to spinal dysraphism who underwent LUTR, became pregnant, and had a CD at our institution from July 2001 to June 2016. We collected data on demographics, hydronephrosis, symptomatic urinary tract infection, continence, and catheterization during pregnancy. CD data included gestational age, abdominal or uterine incisions, and complications. RESULTS We identified 18 pregnancies in 11 women. Fifteen live newborns were delivered via CD (53.3% term births). Thirteen of 15 patients (86.7%) developed new (10) or worsening (3) hydronephrosis. Six of 13 patients (46.2%) underwent nephrostomy tube placement. Eight of 15 patients (53.3%) developed difficulty catheterizing (66.7% via native urethra, 44.4% via catheterizable channel); 50.0% of patients required an indwelling catheter. Five of 15 patients (33.3%) developed urinary incontinence during pregnancy. Ten of 15 patients (66.7%) had a urinary tract infection (30.0% febrile). A urologist was present for all CDs: 5 were scheduled, 10 occurred emergently. Complications occurred in 40.0% (5 cystotomies, 1 bowel deserosalization, 1 vaginal laceration). All cystotomies occurred during emergent CD. Three patients (20.0%) developed urinary fistulae after emergent CD. CONCLUSIONS Women with NB and LUTR have high rates of complications during pregnancy and CD, despite routine involvement of urologists. Women with prolonged labor, previous CD, or those with a history of noncompliance developed the worst complications. Based on our experience, a urologist should always be present and participate in the CD.

Prevalence of maternal cell contamination in amniotic fluid samples

Abstract Purpose: The purpose of this study is to evaluate the incidence of maternal cell contamination (MCC) in the first few milliliters of amniotic fluid withdrawn during amniocentesis. Methods: A prospective observational study was performed. The initial 2–3 ml of amniotic fluid withdrawn during amniocentesis was divided into direct analysis (uncultured) and cultured samples. A matching maternal buccal swab was obtained for MCC testing. MCC was determined by short-tandem repeat analysis. The primary outcome was measurement of clinically significant contamination (MCC >5%). Secondary outcomes included the determination of risk factors associated with MCC >5%. Outcomes were assessed by fisher’s exact, independent t-test, binary logistic regression, and ANOVA. Results: Direct analysis measured clinically significant contamination (MCC > 5%) in 26% of specimens, while any amount of MCC was present in 68% of specimens. Cultured specimens had MCC > 5% in 2%, and any amount of MCC in 24%. Only blood-tinged fluid was associated with an increased risk for MCC > 5%. Larger volumes of the discard sample were not associated with increased incidence of MCC greater than 5%. Conclusion: A significant amount of MCC is present with direct analysis of the initial few milliliters of amniotic fluid withdrawn and is not influenced by the volume of the discard sample. Our results suggest that the first few milliliters of amniotic fluid be removed and discarded when direct analysis is utilized for prenatal genetic testing.

Utility of volumetric assessment of cervical funneling to predict cerclage failure

Abstract Objective: To assess the utility of cervical funnel volume as a predictor of cerclage failure. Methods: We performed a retrospective cohort study of pregnant women with a McDonald cerclage and sonographic evidence of cervical funneling between 1/2008 and 2/2014. Funnel volume (FV) was calculated and used as a correction factor for cervical length (CL) or cerclage height (CH). Receiver operating characteristic (ROC) curves were used to compare the predictive value of CL, CL:FV, CH and CH:FV for cerclage failure at <28 or <34 weeks. CL:FV was further stratified to the <5th, <10th and >10th percentiles and analyzed for prediction of preterm delivery. Results: Subjects with cerclage failure (n = 30) delivered at a mean gestational age of 29.8 +/− 5.3 weeks compared to 38.1+/− 1.39 weeks in those without failure (n = 27; p < 0.001). ROC curves demonstrated CL:FV was the best predictor of delivery <28 weeks (AUC 0.80), while CL was the best predictor of delivery <34 weeks (AUC 0.76). Stratification of CL:FV into <5th versus >10th percentile groups was predictive of early preterm delivery (25.1 weeks versus 34 weeks, p = 0.01). Conclusions: Volumetric assessment of cervical funneling may improve prediction of cerclage failure in the mid-trimester.

The First Report of a Pregnancy in a Patient with Purine Nucleoside Phosphorylase Deficiency

ABSTRACT Background: The cause of primary immunodeficiency has expanded to nearly 200 distinct disorders. An improved understanding of these disorders has resulted in decreased morbidity and mortality with reciprocal improved life expectancy. Obstetricians should have knowledge of primary immunodeficiency, as more women with these disorders will reach reproductive age. Case: 21-year-old G1P0 with purine nucleoside phosphorylase (PNP) deficiency delivered a viable infant vaginally at 37 weeks. Although the patients diagnosis and pregnancy placed her at increased risk for infection, she remained asymptomatic and infection-free throughout pregnancy. Conclusion: The management of pregnancy complicated by PNP deficiency requires strict immune surveillance and regimented immunoglobulin replacement.