David A. Nyberg

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 patients 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. LEVEL OF EVIDENCE: II-2

Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study

Objective To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant. Design Prospective cohort study of 38 033 pregnancies between 1999 and 2003. Setting 15 centres representing major regions of the United States. Participants 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. Main outcome measures Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant. Results For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy. Conclusion Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity.

CESAREAN SECTION BEFORE THE ONSET OF LABOR AND SUBSEQUENT MOTOR FUNCTION IN INFANTS WITH MENINGOMYELOCELE DIAGNOSED ANTENATALLY

Methods. To assess the effect of labor and type of delivery on the level of motor function in fetuses with uncomplicated meningomyelocele, we identified 200 cases of this disorder, accounting for 95 percent of the cases that occurred in the state of Washington during our 10-year study period. We compared the outcomes of 47 infants delivered by cesarean section before labor began, 35 delivered by cesarean section after a period of labor, and 78 who were delivered vaginally (another 40 were ineligible for the study)

First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome.

Objective: To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. Methods: Patients at 10.3–13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12–50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency. Results: There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. Conclusion: First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome. Level of Evidence: II-2

Humerus and femur length shortening in the detection of Down's syndrome

OBJECTIVE Our purpose was to determine the utility of screening for humerus and femur length shortening in prenatal detection of Downs syndrome (trisomy 21). STUDY DESIGN On the basis of the biparietal diameter, predicted humerus and femur lengths were derived from a sample control group of 350 karyotypically normal fetuses. The regression formulas were prospectively applied to 45 consecutive fetuses with Downs syndrome and 942 fetuses with normal karyotypes. Ratios of measured humerus length/predicted humerus length and measured femur length/predicted femur length were calculated for each fetus. RESULTS Eleven of 45 (24.4%) fetuses with Downs syndrome had short humerus (measured humerus length/predicted humerus length ratio of < or = 0.89), and 11 (24.4%) had short femur (measured femur length/predicted femur length ratio of < or = 0.91. In comparison, among 942 karyotypically normal fetuses only 43 (4.5%) showed short humerus and 44 (4.7%) showed short femur (p < 0.05). Fetuses with both short humerus and short femur carried an 11-fold greater risk of Downs syndrome (risk ratio = 11.1; 95% confidence interval = 5.0 to 25.0). CONCLUSION Prenatal ultrasonographic detection of short humerus to short femur, or both significantly increase the risk of Downs syndrome; this information may be useful in screening programs.

Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth.

The “stuck twin” phenomenon: Ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses

Abstract Thirteen consecutive twin pregnancies affected by the “stuck twin” phenomenon were reviewed to determine the potential benefit of serial amniocenteses. The fetal survival rate for the eight pregnancies that underwent serial amniocenteses was 69% (11 of 16 fetuses). This is significantly improved compared with a fetal survival rate of 20% among the five preceding pregnancies managed without serial amniocenteses at the same institution (p = 0.01). It is also markedly improved compared with a combined fetal survival rate of 16% among 48 previously reported pregnancies with the stuck twin phenomenon managed without serial amniocenteses (p

Prenatal sonographic findings of trisomy 18: review of 47 cases.

Prenatal sonographic findings were reviewed in 47 consecutive fetuses with trisomy 18. One or more abnormalities, excluding choroid plexus cysts, were found in 39 fetuses (83%), including 21 of 29 (72%) fetuses examined between 14 and 24 weeks and all 18 (100%) fetuses examined after 24 weeks. Abnormalities most frequently detected before 24 weeks included cystic hygromas, nuchal thickening, and meningomyelocele. Intrauterine growth retardation, cardiac defects, and an enlarged cisterna magna were detected more frequently after 24 weeks than before 24 weeks (P < 0.05). Intrauterine growth retardation was the single most common abnormality, detected in 51% of all fetuses and 89% of fetuses examined after 24 weeks. Choroid plexus cysts were identified in 25% (12 of 47) of fetuses, including 11 of 29 (38%) fetuses seen before 24 weeks. Additional abnormalities were identified in 10 of 12 (83%) fetuses with choroid plexus cysts; one of the two remaining fetuses showed clenched hands and a cardiac anomaly at autopsy, and the other showed unusually large, multiple choroid plexus cysts. Awareness of the type of anomalies and the usual menstrual age of diagnosis in fetuses with trisomy 18 should improve patient counseling and prenatal detection of fetuses considered at risk for this disorder.

Disappearing fetal lung masses: importance of postnatal imaging studies

Background. The “disappearance” of congenital masses of the lung on prenatal sonograms has been described, but the importance of postnatal imaging studies in these children is unknown. Objective. The objective of this work was to study the utility of radiographs and CT scans in asymptomatic infants with congenital masses of the lung that partially or completely resolve on prenatal sonograms performed late in gestation. Materials and methods. The prenatal sonograms, postnatal imaging studies, surgical findings, and pathologic diagnoses of seven children with an echogenic mass of the lung that improved or disappeared on prenatal sonograms were reviewed. Results. All masses were type II congenital cystic adenomatoid malformation, with features of intralobar sequestration also being found in four. An unsuspected extralobar sequestration adjacent to a left lower lobe mass was found at surgery in one patient. All masses were hyperechoic compared with normal lung on sonograms prior to 32 weeks of gestation, with cysts being seen in four. On scans after 32 weeks, four of the masses had resolved completely and three showed subtle increased echogenicity compared with normal lung. Cysts completely resolved in two of four cases. Postnatal radiographs showed subtle abnormalities in four infants, a hyperlucent lobe in one, a soft tissue mass with adjacent hyperlucency in one, and normal findings in one. CT scans were abnormal in all cases, with air-filled cysts and soft tissue in six and a hyperinflated lobe in one. Conclusion. Children with “disappearing” fetal lung masses have persistent abnormalities after birth that are often subtle on radiographs but are well demonstrated with CT.

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.