Stephen Contag

Migraine during pregnancy: is it more than a headache?

Migraine headaches have a female predominance with a peak in prevalence in the third and fourth decades of life. Women of reproductive age are liable to develop their first migraine while pregnant or exhibit changes in the character, frequency or severity of their headaches during pregnancy and the puerperium. The purpose of this Review is to examine the pathophysiology underlying the development of migraine headaches and the association of this pathophysiology with pregnancy-related complications. We also discuss the diagnosis and management of migraine headaches that precede pregnancy or develop de novo during pregnancy, placing an emphasis on the distinction between primary migraine headache and headache secondary to pre-eclampsia—a relatively frequent complication of pregnancy and the puerperium. We present the case of a woman with a history of migraine headaches before pregnancy, whose symptoms progressed during pregnancy in part because of increasing exposure to narcotic medications. We also review the options for migraine evaluation and treatment, and provide an overview of the risks associated with the different treatment options.

Maternal Preeclampsia and Risk for Cardiovascular Disease in Offspring

Hypertensive disease of pregnancy (HDP) has been associated with elevated lifetime cardiovascular risk, including stroke, myocardial disease, coronary artery disease, and peripheral arterial disease. These two entities share common risk factors such as obesity, insulin resistance, diabetes, and hypertension. This article will evaluate the current literature on the maternal and fetal cardiovascular risks posed by HDP. The landmark study by Barker et al. demonstrated increased cardiovascular risk in growth-restricted infants, which may also be associated with HDP. Research has demonstrated the effects that HDP may have on the vascular and nephron development in offspring, particularly with respect to endothelial and inflammatory markers. In order to control for confounding variables and better understand the relationship between HDP and lifetime cardiovascular risk, future research will require following blood pressure and metabolic profiles of the parturients and their offspring.

Pregnancy complicated by triploidy: A comparison of the three karyotypes

We evaluated triploid pregnancy to determine whether there are clinically important differences between the three karyotypes: 69,XXX, 69,XXY, and 69,XYY. Prospectively maintained cytogenetic databases at five tertiary care centers were retrospectively reviewed over a 10-year period to identify all triploid pregnancies. Targeted ultrasounds were reviewed to identify fetal and placental findings. Sonographic findings were compared by karyotype. There was a total of 549 triploid gestations; preimplantation genetic diagnosis (PGD) detected 413 triploid embryos, and the cytogenetic databases provided 136 clinical pregnancies with triploidy. In triploid embryos with PGD, the frequency of the 69,XYY karyotype was 8.7% (36/413), compared with 0.74% (1/136) during the first trimester of clinical pregnancies (p = 0.002). In clinical pregnancies, 60% (36/60) of 69,XXY fetuses survived the first trimester of development compared with 69% (52/75) of 69,XXX fetuses (p = NS). No clinically important differences were observed between 69,XXX and 69,XXY karyotypes in terms of type, number, or severity of fetal or placental anomalies. Gestations with a 69,XYY karyotype are found less frequently compared with gestations with a 69,XXX or 69,XXY karyotype. The decline in fetal survival of the 69,XYY triploid karyotype needs further investigation. There are significant abnormalities detected during prenatal sonography in most all clinically recognized cases of triploidy. Sonography cannot reliably distinguish between the 69,XXY and 69,XXX karyotypes.

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Antenatal corticosteroids may have long-term effects on renal development which have not been clearly defined. Our objective was to compare the responses to intrarenal infusions of ANG II in two groups of year-old, male sheep: one group exposed to a clinically relevant dose of betamethasone before birth and one not exposed. We wished to test the hypothesis that antenatal steroid exposure would enhance renal responses to ANG II in adult life. Six pairs of male sheep underwent unilateral nephrectomy and renal artery catheter placement. The sheep were infused for 24 h with ANG II or with ANG II accompanied by blockade of the angiotensin type 1 (AT(1)) or type 2 (AT(2)) receptor. Baseline mean arterial blood pressure among betamethasone-exposed sheep was higher than in control animals (85.8 +/- 2.2 and 78.3 +/- 1.0 mmHg, respectively, P = 0.003). Intrarenal infusion of ANG II did not increase systemic blood pressure (P >/= 0.05) but significantly decreased effective renal plasma flow and increased renal artery resistance (P < 0.05). The decrease in flow and increase in resistance were significantly greater in betamethasone- compared with vehicle-exposed sheep (betamethasone P < 0.05, vehicle P >/= 0.05). This effect appeared to be mediated by a heightened sensitivity to the AT(1) receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. AT(1) blockade was followed by a significant rebound after 24 h in both groups. AT(2) blockade blunted the 24-h rebound effect among the vehicle-exposed sheep compared with the betamethasone-exposed sheep. In conclusion, antenatal corticosteroid exposure appears to modify renal responsiveness to ANG II by increasing AT(1)- and decreasing AT(2) receptor-mediated actions particularly as related to renal blood flow and sodium excretion.

Sex-specific effect of antenatal betamethasone exposure on renal oxidative stress induced by angiotensins in adult sheep

Prenatal glucocorticoid administration in clinically relevant doses reduces nephron number and renal function in adulthood and is associated with hypertension. Nephron loss in early life may predispose the kidney to other insults later but whether sex influences increases in renal susceptibility is unclear. Therefore, we determined, in male and female adult sheep, whether antenatal glucocorticoid (betamethasone) exposure increased 8-isoprostane (marker of oxidative stress) and protein excretion after acute nephron reduction and intrarenal infusions of angiotensin peptides. We also examined whether renal proximal tubule cells (PTCs) could contribute to alterations in 8-isoprostane excretion in a sex-specific fashion. In vivo, ANG II significantly increased 8-isoprostane excretion by 49% and protein excretion by 44% in male betamethasone- but not in female betamethasone- or vehicle-treated sheep. ANG-(1-7) decreased 8-isoprostane excretion but did not affect protein excretion in either group. In vitro, ANG II stimulated 8-isoprostane release from PTCs of male but not female betamethasone-treated sheep. Male betamethasone-exposed sheep had increased p47 phox abundance in the renal cortex while superoxide dismutase (SOD) activity was increased only in females. We conclude that antenatal glucocorticoid exposure enhances the susceptibility of the kidney to oxidative stress induced by ANG II in a sex-specific fashion and the renal proximal tubule is one target of the sex-specific effects of antenatal steroids. ANG-(1-7) may mitigate the impact of prenatal glucocorticoids on the kidney. P47 phox activation may be responsible for the increased oxidative stress and proteinuria in males. The protection from renal oxidative stress in females is associated with increased SOD activity.

Contemporary management of migrainous disorders in pregnancy.

Purpose of review Migraine is a frequent event among women of reproductive age. It is difficult to predict the course and severity of disease that migraineurs will endure during pregnancy. Treatment is often compromised during pregnancy because of concerns regarding pharmacotherapy and fetal well being. Recent findings The majority of women with migraine during pregnancy will not require ongoing pharmacotherapy or prophylaxis. Nonpharmacologic strategies should be the first-line treatment of migraines. For severe migraines, recent cohort studies documenting the use of triptans for treatment during pregnancy have shown no increase in adverse pregnancy and fetal outcomes above the average rate. High-dose valproate is the only antiepileptic drug available for migraine prophylaxis that has been shown to cause long-term cognitive effects in infants exposed during gestation. Congenital syndromes have been described for most of the older antiepileptic drugs but less so for many of the newer drugs. These newer medications appear to have improved safety profiles for use in pregnancy but there is still information lacking from larger patient cohorts and longitudinal studies of neurodevelopmental outcomes. There is also evidence to support use of beta-blockers and calcium-channel blockers for migraine prevention during pregnancy. Summary For those patients who develop debilitating migraine or whose migraines interfere with activities of daily living, there are several options for treatment and headache prevention that have a low likelihood of compromising fetal well being.

Sonographic Findings in Trisomy 9

Objective. The purpose of this study was to identify the most common prenatal sonographic findings in fetuses with complete trisomy 9. Methods. A retrospective review of all cases of trisomy 9 at 5 participating institutions over a 15‐year interval was conducted. Indications for referral and sonographic findings in each case were reviewed to identify characteristic fetal structural anomalies. Results. Six cases of trisomy 9 are presented. Most patients were referred for abnormal sonographic findings on screening examinations (66%) or advanced maternal age (33%). Fetal heart defects and central nervous system malformations were the most frequent sonographic anomalies seen. Conclusions. Sonographic findings in trisomy 9 are similar to those found in other autosomal trisomies. Because trisomy 9 is uniformly lethal and is not included as part of the standard prenatal aneuploidy screening by fluorescence in situ hybridization analysis, clinicians should be cautious in counseling patients with structurally abnormal fetuses until the full karyotype is available.

Antenatal betamethasone exposure alters renal responses to angiotensin-(1–7) in uninephrectomized adult male sheep

Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1–7) in rams and the angiotensin receptors involved in mediating responses to the peptide. Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1–7) infusions (1 ng/kg/min) alone or in combination with antagonists to angiotensin receptors for 3 h. Basal sodium excretion (UNa) was significantly lower and mean arterial pressure was significantly higher in betamethasone- compared to the vehicle-treated sheep. Angiotensin-(1–7) decreased UNa more in betamethasone- than in vehicle-treated sheep. Candesartan reversed the response to angiotensin-(1–7) but D-Ala7-angiotensin-(1–7) did not. Angiotensin-(1–7) infusion decreased effective renal plasma flow in both groups to a similar extent and the response was reversed by candesartan, but was not blocked by D-Ala7-angiotensin-(1–7). Glomerular filtration rate increased significantly in both groups after 3 h infusion of angiotensin-(1–7) plus candesartan. These results suggest that antenatal exposure to a clinically relevant dose of betamethasone impairs renal function in rams. Moreover, angiotensin-(1–7) appears capable of activating the AT1R in uninephrectomized rams.

Ultrasound findings in trisomy 22.

We sought to identify the characteristic sonographic findings of fetal trisomy 22 by performing a retrospective review of nine cases of fetal trisomy 22. All cases of chromosomal mosaicism were excluded, as were first-trimester losses. Indications for sonography, gestational age, and sonographically detected fetal anomalies were analyzed. The majority of patients were referred for advanced maternal age or abnormal ultrasound findings on screening exam. Oligohydramnios was the most common sonographic finding, present in 55% of affected fetuses. Intrauterine growth restriction and increased nuchal thickness were slightly less frequent.

Association of maternal obesity with maternal and neonatal outcomes in cases of uterine rupture

OBJECTIVE To describe the risk of adverse outcomes associated with uterine rupture in the setting of maternal obesity. METHODS This was a retrospective cohort analysis of singleton nonanomalous neonates born after uterine rupture between 34 and 42 weeks of gestation. We derived data from the U.S. Natality Database from 2011 to 2014. Maternal prepregnancy body mass index (BMI) was categorized according to the World Health Organization classification. The rates of neonatal and maternal complications were calculated for each BMI class. Multivariable logistic regression analysis was used to estimate the risks of these complications among obese pregnancies compared with normal-weight pregnancies. RESULTS There were 3,942 cases of uterine rupture identified among 15,860,954 births (0.02%) between 2011 and 2014. Of these, 2,917 (74%) met inclusion criteria for analysis. There was an increased risk of low 5-minute Apgar score (22.9% compared with 15.9%; adjusted odds ratio [OR] 1.49 [1.19-1.87]), neonatal intensive care unit admission (31% compared with 24.6%; adjusted OR 1.51 [1.23-1.85]), and seizure (3.7% compared with 1.9%; adjusted OR 1.80 [1.05-3.10]) in obese compared with normal-weight pregnancies. The rate of prolonged assisted ventilation was 8.5% compared with 6.2% (P=.13), which, after adjustment for confounders, was a statistically significant difference (adjusted OR 1.47 [1.05-2.07]). The rate of neonatal death was similar (12.4 compared with 6.5/1,000 births; adjusted OR 2.03 [0.81-5.05]). The rates of various maternal complications were similar between groups. CONCLUSION In the setting of uterine rupture, maternal obesity moderately increases the risks of low Apgar score, neonatal intensive care unit admission, prolonged ventilation, and seizure. Risk of maternal complications and the risk of neonatal death, however, are similar to risks in patients of normal BMI.