Pregnancy after age 50: defining risks for mother and child.

Assisted reproductive technology using donor-egg in vitro fertilization (D-IVF) has enabled women 50 years and above to successfully achieve pregnancy. We examine the safety profile of these pregnancies through a large, single-center case series and retrospective cohort analysis in which all participants were carefully screened medically prior to conception. Consecutive women aged ≥ 50 years (n = 101) who achieved a viable pregnancy via D-IVF were identified and their perinatal outcomes were recorded. These data were compared with control data from younger (≤ 42 years) recipients of D-IVF (n = 41) who also achieved a viable pregnancy at our center during the same period. Compared with the younger women, older recipients had statistically similar rates of hypertensive disorders of pregnancy (23% versus 14%, odds ratio [OR] 1.9 [0.65 to 5.4]), gestational diabetes (4.0% versus 3.0%, OR 1.4 [0.15 to 113.0]), preterm premature rupture of membranes/preterm labor (8.9% versus 14%, OR 0.59 [0.18 to 1.9]), and abnormal placentation (2.1% versus 0%). Cesarean delivery was high in women ≥ 50 (81% of singletons, 100% of multiples). There was one maternal death, which occurred before delivery in a 49-year-old woman who would have been 50 at term had she survived, presumably secondary to myocardial infarction. Primary neonatal outcomes of gestational age and birth weight were excellent and similar between groups. Women ≥ 50 years who achieve pregnancy via D-IVF are at high risk for maternal complications, particularly hypertensive disorders and cesarean section, but at rates similar to those seen in younger recipients.

The association of elective cessation of tocolysis and preterm birth in singleton gestations.

We evaluated outcomes following tocolysis discontinuation in singleton pregnancies between 33.0 and 36.9 weeks' gestation. We performed a retrospective analysis of singleton pregnancies prescribed continuous subcutaneous terbutaline tocolysis. Patients without indicated preterm delivery discontinuing treatment between 33.0 and 36.9 weeks were evaluated ( N = 4253). Data were grouped by week at treatment discontinuation. Outcomes were compared for each week. Approximately 55% (2316/4253) delivered preterm (< 37 weeks). After treatment discontinuation, 58.1% (2472/4253) of patients delivered within 7 days and 41.2% (1752/4253) within 3 days. Median number of days from discontinuation to delivery was 5 (range, 0 to 65). Incidence of low birth weight (< or = 2500 g), neonatal intensive care unit admissions, days in nursery, and estimated charges decreased with each additional week of tocolysis (all P < 0.05, adjusted for multiple comparisons). Tocolysis discontinuation prior to term is associated with late-preterm birth, adverse neonatal outcomes, and increased estimated health care costs.

Variability in thyroid-stimulating hormone suppression by human chorionic [corrected] gonadotropin during early pregnancy.

OBJECTIVE: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation. STUDY DESIGN: The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study. RESULTS: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11-13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15-18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations. CONCLUSIONS: In early pregnancy, a woman's centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately.

Maternal thyroid hypofunction and pregnancy outcome.

OBJECTIVE: To estimate whether maternal thyroid hypofunction is associated with complications. METHODS: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used. RESULTS: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P<.001, respectively). CONCLUSION: Maternal thyroid hypofunction is not associated with a consistent pattern of adverse outcomes. LEVEL OF EVIDENCE: II.

First-trimester screening with nasal bone in twins.

OBJECTIVE: The purpose of this study was to evaluate the Down syndrome detection rate at a 5% screen positive rate in first-trimester screening for twins. STUDY DESIGN: This was a retrospective study from August 2005 to July 2007 of twins who underwent first-trimester screening with nuchal translucency, nasal bone, pregnancy-associated plasma protein-A, and free beta-hCG. Risks were calculated on the basis of the Fetal Medicine Foundation twin algorithm. The model simulated distributions of unaffected and affected cases at 12 weeks of gestation. RESULTS: Two thousand ninety-four twin pregnancies (4188 fetuses) met the inclusion criteria. The addition of nasal bone to nuchal translucency, pregnancy-associated plasma protein-A, and free beta-hCG increased the Down syndrome detection rate from 79-89% at a 5% screen-positive rate. CONCLUSION: In twins, first-trimester screening with nasal bone is valuable. The improved Down syndrome detection rate can help these high-risk patients with the decision-making process of whether to pursue invasive testing with its associated pregnancy loss risk.

First- and second-trimester thyroid hormone reference data in pregnant women: a FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study.

OBJECTIVE: The purpose of this study was to calculate first and second trimester reference ranges and within-woman correlations for TSH, free T4, and thyroid antibodies. STUDY DESIGN: TSH, free T4, and thyroid antibodies were measured in paired sera from 9562 women in the FaSTER trial of Down syndrome screening. RESULTS: The median first trimester TSH (1.05 mIU/L) is lower than the second (1.23 mIU/L); and 98th centile is higher (4.15 vs 3.77 mIU/L). Within-woman paired TSH correlations are moderately strong (r(2) = 0.64). Among women with first trimester TSH values above the 98th centile, second trimester values are over the 95th centile in 68%. Median first trimester free T4 values (1.10 ng/dL) are higher than second (1.01 ng/dL). Paired free T4 measurements correlate weakly (r(2) = 0.23). Among women with first trimester free T4 values below the 2nd centile, second trimester values are below the 5th centile in 32%. Antibody measurements correlate strongly between trimesters (thyroperoxidase r(2) = 0.79, thyroglobulin r(2) = 0.83). CONCLUSION: TSH and free T4 measurements require gestation-specific reference ranges.

Sequential first- and second-trimester TSH, free thyroxine, and thyroid antibody measurements in women with known hypothyroidism: a FaSTER trial study.

OBJECTIVE: The purpose of this study was to examine how closely hypothyroidism management in the general pregnancy population satisfies recently issued guidelines and to determine whether improvements are indicated. STUDY DESIGN: This was an observational study in which women at 5 recruitment centers in the first- and second-trimester evaluation of risk for aneuploidy trial allowed the use of sequentially obtained first- and second-trimester sera for additional research. Three hundred eighty-nine women had hypothyroidism by self-report. Thyroid-related measurements were performed on all samples between July 2004 and May 2005. RESULTS: Forty-three percent of the thyroid-stimulating hormone (TSH) values are at or above recently recommended guidelines in the first trimester (2.5 mU/L), as opposed to 33% of the values in the second trimester (3.0 mU/L). Twenty percent of the TSH values are at or above a less restrictive 98th percentile of normal in the first trimester, as opposed to 23% of the values in the second trimester. Mean TSH levels are higher in women with antibodies. Free thyroxine values are unremarkable. CONCLUSION: Future strategies should focus on more effectively treating women with hypothyroidism who have persistently elevated TSH values.

Growth abnormalities and multiple gestations.

Growth abnormalities which include intrauterine growth restriction and weight discordance between twins are common in pregnancies complicated by multiple gestations and may be associated with poor perinatal outcomes. Knowledge of chorionicity is paramount when managing a multiple pregnancy. Monochorionic twins are at greater risk than dichorionic twins for growth issues, which may result in long-term complications including adverse neurological sequelae for the offspring. The purpose of the following article is to define normal and abnormal growth in multiples. In addition, the management of growth abnormalities in relationship to chorionicity will be discussed.

The association between vasa previa, multiple gestations, and assisted reproductive technology.

Patients with multiple gestations, low-lying placentas, velamentous cord insertions, and history of assisted conception should be evaluated carefully for a vasa previa. Serial surveillance for signs of preterm labor and elective cesarean delivery at 34 to 35 weeks after corticosteroids for fetal lung maturity is a reasonable management strategy for vasa previa in multiple gestations.

Thrombophilia and the obstetric patient.

OBJECTIVE: To examine how practicing obstetricians evaluate and manage thrombophilias in selected clinical situations. METHODS: A questionnaire investigating knowledge and practice patterns pertaining to thrombophilia was mailed to 300 randomly selected American College of Obstetricians and Gynecologists Fellows and Junior Fellows in February 2005. RESULTS: Approximately 50% (151) of questionnaires were returned. Statistical analysis focused on the 104 responding obstetricians. The majority (greater than 70%) know which thrombophilias are inherited and which are acquired. More than 50% send an inherited thrombophilia panel and antiphospholipid antibodies on patients with a history of fetal demise, intrauterine growth restriction (less than 5th percentile), abruption, and severe preeclampsia. Ninety-two percent test patients with recurrent miscarriages for antiphospholipid antibodies. Despite no clear evidence, 80% also test these patients for inherited thrombophilias. The majority intervene with either thromboprophylaxis or low-dose aspirin when managing patients at risk for thromboembolism. Seventy percent use low-molecular-weight (fractionated) heparin for patients requiring therapeutic anticoagulation, while 62% also use it for prophylactic anticoagulation. Thirty-eight percent of physicians using low-molecular-weight (fractionated) heparin monitor anti-factor Xa levels. The majority (56%) felt their residency training with regard to thrombophilia was barely adequate. Only 8% felt their training was comprehensive, while 36% felt it was adequate. CONCLUSION: Most responding obstetricians do not manage thrombophilia patients according to expert opinion. Despite the fact that often there is no clear evidence for treatment, many physicians are inclined to intervene in patients at risk for thromboembolism. Educational endeavors are needed to guide obstetricians caring for patients at risk for thromboembolism. LEVEL OF EVIDENCE: III.

Screening for Down syndrome: practice patterns and knowledge of obstetricians and gynecologists.

OBJECTIVE: To assess obstetricians' practice patterns and knowledge regarding screening for Down syndrome. METHODS: A questionnaire was mailed to 1,105 American College of Obstetricians and Gynecologists Fellows and Junior Fellows in 2004. RESULTS: Sixty percent of questionnaires were returned. Statistical analyses were limited to the 532 practicing obstetricians. Greater than 80% felt their training and experience qualified them to counsel patients about genetic issues in pregnancy. However, 45% rated their residency training regarding prenatal diagnosis as barely adequate or nonexistent. American College of Obstetricians and Gynecologists publications were rated by 86% as an important source of information on genetic counseling. Seventy-eight percent of practitioners counsel all obstetric patients about risks for fetal aneuploidy, and 67% provide counseling for heritable genetic abnormalities. Although the majority (99%) offer second-trimester Down syndrome screening, only 55% also offer first-trimester screening for Down syndrome. Almost one half (49%) use the quad screen, and 6% offer integrated first- and second-trimester screening. The majority (88%) routinely offer amniocentesis to patients who are at elevated risk for genetic abnormalities, whereas 44% also offer chorionic villus sampling. Few (2%) perform chorionic villus sampling. CONCLUSION: Most obstetricians manage patients at risk for fetal genetic abnormalities according to American College of Obstetricians and Gynecologists educational materials. This survey identified deficiencies related to Down syndrome screening, including a limited number of practitioners performing chorionic villus sampling and physicians' own perception that training regarding genetic counseling should be improved. Educational strategies are needed to address these deficiencies before first-trimester screening programs are widely implemented. LEVEL OF EVIDENCE: III.

Antenatal sonographic prediction of twin chorionicity.

OBJECTIVE: We sought to determine the accuracy of antenatal diagnosis of twin chorionicity at a single tertiary care center and assess the consequences of incorrect diagnoses. STUDY DESIGN: Twins with chorionicity diagnosed by ultrasound < or = 24 weeks' gestation were retrospectively reviewed. Chorionicity was assigned by sonographic findings including placental location(s), the lambda and T-signs, and/or fetal gender(s). Postnatal diagnosis was determined by placental histopathologic examination. Medical records of antenatal-postnatal discordant chorionicities were reviewed for adverse sequelae. RESULTS: Chorionicity was correctly assigned antenatally in 392/410 (95.6%) twins. The sensitivity, specificity, and positive and negative predictive values of monochorionicity assessed < or = 14 weeks were 89.8%, 99.5%, 97.8%, and 97.5%. Corresponding statistical values for the second trimester were 88.0%, 94.7%, 88.0%, and 94.7%. Two cases of inaccurate antenatal diagnoses affected patient counseling or were associated with adverse clinical outcomes. CONCLUSION: Antenatal assessment of chorionicity is accurate; however, incorrect diagnoses do occur and can affect reliable patient counseling and management.

Multiple gestations and late preterm (near-term) deliveries.

Multiple gestations present unique challenges to the modern obstetrician. Many twin and high-order multiple pregnancies are delivered between 34 and 37 weeks' gestation either secondary to preterm labor or obstetrical complications necessitating intervention. Recognizing the increasing prevalence of multiple gestations and the impact of late preterm deliveries in modern practice, this review analyzes the impact of multiple pregnancies on perinatal outcomes, reviews the strategies to prevent preterm labor, and summarizes potential indications for late preterm delivery. In this paper, "late preterm" has been used instead of "near-term," as the former was considered more appropriate to reflect this subgroup of preterm infants in a workshop on this topic held in July 2005, organized by the National Institute of Child Health and Human Development.

The impact of multiple gestations on late preterm (near-term) births.

Multiple pregnancies currently account for 3% of all births in the United States but are disproportionately responsible for larger rates of prematurity and significant neonatal morbidity. The mean birth age for most multi-fetal pregnancies occurs during the late preterm period when both spontaneous preterm labor and iatrogenic premature birth because of obstetrical or maternal complications are common. Multiples pose numerous unique challenges, emphasizing the significant impact of plurality on late preterm births.

Prophylactic ephedrine and combined spinal epidural: maternal blood pressure and fetal heart rate patterns.

OBJECTIVE: Labor analgesia with the combined spinal epidural approach has been associated with maternal hypotension and fetal heart rate (FHR) changes. The purpose of this study was to estimate whether prophylactic intramuscular ephedrine before combined spinal epidural prevents these complications. METHODS: In a prospective double blind trial, 100 healthy patients with term singletons received intramuscular ephedrine 25 mg or placebo by random allocation before combined spinal epidural. During the first hour after analgesia, maternal heart rate, blood pressure, and need for treatment of significant hypotension were recorded. Fetal heart rate tracings for 1 hour before and for 1 hour after administration of anesthetic were evaluated. Categorical variables were compared with Fisher exact test. Continuous variables were compared with one way analysis of variance for repeated measures. P < .05 was considered significant. RESULTS: Prophylactic ephedrine reduced the incidence of maternal hypotension after combined spinal epidural (P < .007). In controls, there was a significant increase in the incidence and frequency of late decelerations in the hour following combined spinal epidural compared with the previous hour (P < .005 and P < .01). Compared with controls, there was an increased incidence of fetal tachycardia in patients who received prophylactic ephedrine (P < .006), which was associated with increased FHR reactivity (P < .03). CONCLUSION: Although prophylactic ephedrine prevents maternal hypotension and fetal late decelerations, it is associated with fetal tachycardia. The value of prophylactic ephedrine at combined spinal epidural should be weighed against potential changes in fetal heart rate patterns. LEVEL OF EVIDENCE: I.

Impact of maternal age on obstetric outcome.

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.

First trimester screening for Down syndrome in multiple pregnancy.

The incidence of twins, triplets, and high-order multiples has increased substantially in the last two decades secondary to fertility treatments and to delayed childbearing. Prenatal diagnosis in these patients is challenging. Options for screening tests are limited. First trimester screening for Down syndrome in patients with multiples appears promising. This paper will review the advantages of first trimester screening in this high-risk patient population.

First and second trimester evaluation of risk for fetal aneuploidy: the secondary outcomes of the FASTER Trial.

The FASTER Trial was a multicenter National Institute of Child Health and Human Development sponsored study of Down syndrome screening in a large unselected obstetric population using first and second trimester maternal serum markers and first trimester nuchal translucency sonography. The following paper will describe the FASTER Trial. It will review the outcomes of pregnancies complicated by cystic hygroma and the FASTER Trial's findings regarding first trimester nasal bone ultrasonography and screening for aneuploidy. Although the study's first and foremost goal was to compare various first and second trimester methods of screening for Down syndrome, the FASTER Trial has revealed a wealth of information not only on screening for aneuploidy but also on other obstetric issues.

Education and quality review for nuchal translucency ultrasound.

First trimester nuchal translucency ultrasound has evolved from an ultrasound measurement used only in a research setting to a screening tool which is being offered to the general obstetric population. Studies of nuchal translucency suggest great variation in Down syndrome detection rates which may be secondary to significant differences in sonographic training and nuchal translucency image quality. Inaccurate screening has the potential to adversely impact patients. This paper will explore: (1) why quality review in nuchal translucency ultrasound is important, (2) methods of nuchal translucency quality assessment, (3) experience with quality review in the research setting, and (4) current strategies for quality assessment in patient care.

Additional benefits of first trimester screening.

The goal of first trimester screening for aneuploidy is to provide patients their risk assessment for fetal Down syndrome. Nonetheless, it has been noted that combined screening offers physicians and patients other important pregnancy information. For example, first trimester ultrasound results in accurate pregnancy dating and enables the early diagnosis of multiple gestations during the period when amnionicity and chorionicity is best discerned. It also detects a limited number of fetal anatomical abnormalities, affording patients time to make decisions regarding the management of their pregnancies. A cystic hygroma, one of the most powerful ultrasound markers for fetal aneuploidy, can be detected on first trimester ultrasound. An enlarged nuchal translucency may identify fetuses at risk for other adverse outcomes and for congenital heart defects. In addition, abnormal first trimester serum markers are associated with adverse pregnancy outcomes, and knowledge of these abnormalities may help with patient counseling and management.