Is severe macrosomia manifested at 11-14 weeks of gestation?

OBJECTIVE: To determine the association between fetal biometry in the first or early second trimester and severe macrosomia at delivery. METHODS: This case-control study included 30 term severely macrosomic neonates; 90 appropriate-for-gestational age (AGA) neonates served as controls. All pregnancies underwent nuchal translucency (NT) screening at 11-14 weeks' gestation. Pregnancies were dated by accurate last menstrual period consistent with crown-rump length (CRL) measurements at the time of screening, early pregnancy CRL or date of fertilization. The association between birth weight and the difference between the measured and the expected CRL at the time of NT screening was analyzed. RESULTS: The difference between measured and expected CRL, expressed both in mm and in days of gestation, was statistically greater in the severely macrosomic neonates compared with controls (mean, 6.66 +/- 4.78 mm vs. 1.17 +/- 4.6 mm, P < 0.0001 and 3 +/- 2.2 days vs. 0.5 +/- 2.3 days, P < 0.0001, respectively). Furthermore, there were significant correlations between the extent of macrosomia and the discrepancy between expected and measured fetal size at the time of NT screening (r = 0.47, P < 0.01 and r = 0.48, P < 0.01, respectively). CONCLUSION: Severe macrosomia apparently manifests as early as 11-14 weeks' gestation.

Does the availability of maternal HbA1c results improve the accuracy of sonographic diagnosis of macrosomia?

OBJECTIVE: To determine whether measuring maternal glycosylated hemoglobin (HbA1c) can improve the accuracy of sonographic estimation of fetal macrosomia. METHODS: Sonographic estimation of fetal weight (EFW) and maternal HbA1c were obtained in term, non-diabetic patients within 1 week before delivery. Neonatal birth weights were recorded at delivery and compared with both sonographic estimations and HbA1c. Macrosomia was defined as birth weight of >or=4000 g. The absolute error of the sonographic EFW was calculated. Receiver-operating characteristics (ROC) curve analysis was used to evaluate sonographic EFW and HbA1c as predictors of birth weight >or=4000 g. Variables were tested using regression analysis and student's t-test. RESULTS: One hundred and sixty two patients were evaluated between July and December 2002. Twenty-eight patients (17.3%) delivered macrosomic infants. Sonographic EFW >or=4000 g predicted macrosomia with sensitivity, specificity and positive and negative predictive values of 66.6%, 88.8%, 54.5% and 93.0%, respectively. Its overall accuracy was 85.5%. The area under the ROC curve of sonographic EFW in the prediction of macrosomia was 0.9 (P < 0.001). HbA1c levels in women delivering macrosomic and non-macrosomic neonates were 5.3 +/- 0.7% and 5.2 +/- 0.5%, respectively (P = 0.27). The area under the ROC curve of HbA1c in the prediction of macrosomia was 0.53 (P = 0.27). CONCLUSIONS: Maternal HbA1c is not a useful test in the prediction of birth weight. It therefore cannot be used to improve the accuracy of sonographic EFW.

Inferior vena cava thrombosis presenting as non-immune hydrops in the fetus of a woman with diabetes.

We present a rare case of non-immune hydrops fetalis (NIHF) caused by a thrombus in the inferior vena cava in a neonate with low levels of anti-thrombin III. The diagnosis of (NIHF) was made in utero in a 43-year-old woman with poorly controlled gestational diabetes who subsequently developed pre-eclampsia. Cesarean section was performed due to fetal compromise and worsening pre-eclampsia. The thrombus resolved after neonatal treatment with heparin.

Nucleated red blood cells in human fetal scalp capillary blood samples: a feasibility study.

OBJECTIVE: Elevated umbilical cord nucleated red blood cell (NRBC) counts have been suggested as a predictor of adverse perinatal outcome. We sought to evaluate the feasibility of obtaining fetal scalp capillary blood NRBC counts during labor and to assess their correlation with umbilical cord NRBC counts. METHODS: Fetal scalp capillary blood specimens were prospectively collected in laboring patients who underwent scalp sampling because of the presence of an abnormal fetal heart rate pattern. Matched umbilical cord blood samples were collected immediately after birth. Outcome measures were the feasibility of obtaining fetal scalp NRBC counts and their correlation with umbilical cord NRBC counts. RESULTS: Thirteen term singleton pregnancies formed the study population. In four patients, fetal scalp capillary blood sampling was performed twice. Of the attempts to evaluate fetal scalp capillary samples for NRBC counts, 16 out of 17 (94.1%) were successful. The mean fetal scalp capillary blood NRBC count per 100 white blood cells was 12.6 +/- 7.6 (+/- SD). Umbilical cord mixed, venous and arterial NRBC counts were 15.5 +/- 8.8, 13.4 +/- 10.7 and 12.6 +/- 10.7, with p = 0.09, p = 0.59 and p = 0.68, respectively, when compared to the corresponding scalp sample. The Spearman rank correlation between fetal scalp capillary samples and umbilical cord mixed, venous and arterial NRBC counts were r = 0.86, r = 0.92 and r = 0.95, respectively, with all p values < 0.001. CONCLUSION: Previous studies have established the clinical utility of umbilical cord NRBC counts. Our study demonstrated that it was possible to obtain NRBC counts from a fetal scalp capillary sample and that these counts correlated highly with umbilical cord NRBC counts. Future studies are needed to evaluate fetal scalp NRBC counts as a predictor of perinatal outcome.

The association between fetal and maternal sleep patterns in third-trimester pregnancies.

OBJECTIVE: We sought to investigate the association between fetal heart rate and maternal electroencephalogram patterns during overnight sleep. STUDY DESIGN: Data were collected prospectively between December 1, 1999, and June 30, 2001. Initially, the participating patients were asked to complete a 66-question survey for the assessment of maternal perception of sleep quality that was referred to as the sleep disturbance score: a continuous score from 0 (no evidence of sleep disturbance) to 110 (extreme sleep disturbance). Second, a subgroup of patients was monitored overnight by concomitant fetal heart rate and maternal electroencephalogram tracings. Statistical analysis included the Student t test, chi2 test, logistic regression, and Cramer's V contingency correlation. RESULTS: One hundred two singleton pregnancies formed the study population. The mean sleep disturbance score was 26.7 +/- 9.9. Maternal age was the only variable that correlated with sleep disturbance score. A subgroup of 11 patients was studied overnight. A significant correlation between active fetal sleep and maternal wakefulness was demonstrated in 6 patients. The mean sleep disturbance score for these patients was significantly higher than for patients without such correlation (P =.04). CONCLUSION: This study establishes an association between fetal activity and maternal wakefulness, which explains many of the maternal awakenings during sleep in the third trimester.

Maternal pain and anxiety in genetic amniocentesis: expectation versus reality.

OBJECTIVE: To investigate maternal perceptions of both pain and anxiety before and after genetic amniocentesis. STUDY DESIGN: This prospective study of midtrimester, singleton pregnancies was conducted between March 2000 and July 2000. Study variables included patient demographics, medical and obstetric histories, indication for amniocentesis and a description of the source of information used by the patient regarding the procedure and technical degree of difficulty. Maternal pain and anxiety associated with performing amniocentesis were subjectively quantified with the use of the visual analog scale (VAS). Statistical analysis included Wilcoxon signed rank test, anova, and simple and stepwise regression analyses. RESULTS: One hundred and eighty-three women participated in the study. Perception of pain before amniocentesis was significantly higher compared to that expressed immediately after the procedure, with a mean VAS score of 3.7 +/- 2.5 vs. 2.1 +/- 2.0 (P < 0.0001). Similarly, perception of anxiety was significantly greater prior to the procedure, with a mean VAS score of 4.6 +/- 2.8 vs. 2.8 +/- 2.4 after the amniocentesis (P < 0.0001). Perceptions of pain and anxiety were significantly and positively correlated to each other both before and after the procedure (P < 0.0001). History of a prior amniocentesis was the only variable associated with reducing expected pain and anxiety (negative correlation, P < 0.001), whereas the technical degree of difficulty was the only significant variable impacting on the actual pain and anxiety (positive correlation, P < 0.005). CONCLUSIONS: Preamniocentesis counseling should emphasize the fact that, for most women, the actual pain and anxiety experienced during the procedure are significantly lower than expected. In fact, on a scale of 0-10, the mean level of pain was only 2.1, with a slightly higher mean level of anxiety.

Non-reassuring fetal status in the prolonged pregnancy: the impact of fetal weight.

OBJECTIVE: To evaluate the incidence of abnormal fetal findings and Cesarean delivery for non-reassuring fetal status as a function of birth weight in the uncomplicated prolonged pregnancy. METHODS: Seven hundred and ninety-two patients at or beyond 41 weeks' gestation were managed expectantly. Population-specific birth-weight percentiles were calculated. Fetuses were retrospectively categorized as small (birth weight < 10th percentile), average (10th percentile < or = birth weight < or = 90th percentile) or large (birth weight > 90th percentile). The incidences of abnormal antepartum fetal testing results (i.e. oligohydramnios and/or abnormal non-stress testing) and Cesarean delivery for intrapartum non-reassuring fetal status were calculated for these three birth-weight categories. RESULTS: There was a significant inverse relationship between the incidence of abnormal fetal testing and birth-weight category (36%, 14% and 9% for small, average and large fetuses, respectively, P < 0.001). Small fetuses were more likely to require a Cesarean delivery for non-reassuring fetal status during labor than were all other fetuses (12.3% vs. 5.3%, P = 0.024). CONCLUSIONS: The frequency of oligohydramnios and abnormal non-stress testing is inversely related to birth weight in the expectantly managed prolonged pregnancy. In addition, small fetuses born at or beyond 41 weeks' gestation have an increased rate of Cesarean delivery for intrapartum non-reassuring fetal status.

The impact of maternal ketonuria on fetal test results in the setting of postterm pregnancy.

OBJECTIVE: The aim of this study was to determine whether ketonuria, a commonly assessed urinary marker of maternal starvation and dehydration, is associated with abnormal fetal test results in the setting of postterm pregnancy. STUDY DESIGN: During a 4-year period (January 1993-December 1996), a total of 3655 visits for antepartum maternal-fetal testing of postterm pregnancies (> or =41 weeks' gestation) occurred at our institution. Maternal assessment included vital signs and urinalysis. The presence and degree of maternal ketonuria was correlated against abnormal results of fetal heart rate tests, nonstress tests, amniotic fluid index measurements, and biophysical profile scores performed on the same day. RESULTS: There were 3601 encounters suitable for inclusion in the study. Clinically detectable ketonuria occurred in 10.9% of the patients studied. Patients with clinically detectable ketonuria were at increased risk relative to patients without ketonuria for abnormal outcomes during postterm testing, including the presence of oligohydramnios (24% vs. 9.3%; P<.0001 ), nonreactive nonstress tests (6.2% vs. 2.15%; P<.0001), and fetal heart rate decelerations (14% vs 9.2%; P =.0039 ). CONCLUSION: Maternal ketonuria among patients with postterm pregnancy was associated with a >2-fold increase in the occurrence of oligohydramnios, a 3-fold increase in nonreactive nonstress tests, and a significant increase in fetal heart rate decelerations. Further studies are required to evaluate the potential benefits of treating ketonuria before fetal testing.

Umbilical artery Doppler velocimetry--an update.

Doppler ultrasonography was introduced into clinical obstetric practice over 20 years ago. It is also accepted that a variety of common obstetrical complications such as preeclampsia and intrauterine growth restriction have their origin in abnormal development of the placental vasculature and this could be reflected in abnormal Doppler velocimetry. Doppler velocimetry of the umbilical artery has been the subject of multiple clinical studies but results have often been disputed due to differences in study populations and methodologies. In recent years, meta-analysis of randomized clinical trials have shown that incorporation of Doppler velocimetry into clinical practice will reduce perinatal mortality in high-risk patients. This article reviews the data of the meta-analyses as it pertains to the management of high-risk pregnant patients.

Nucleated red blood cell count in the differentiation of fetuses with pathologic growth restriction from healthy small-for-gestational-age fetuses.

OBJECTIVE: The purpose of this study was to evaluate the utility of the neonatal nucleated red blood cell count in differentiating the fetus with growth restriction from the small but otherwise healthy fetus. STUDY DESIGN: Perinatal outcomes were evaluated prospectively for all neonates admitted to the neonatal intensive care unit in 1997. Nonanomalous neonates with normal phenotype and a complete blood cell count performed within the first 6 hours after birth were included in the study. All neonates with birth weights lower than the 10th percentile for gestational age were considered small for gestational age. Neonates were divided into four groups: small-for-gestational-age neonates with elevated nucleated red blood cell counts, appropriately grown neonates with elevated nucleated red blood cell counts, small-for-gestational-age neonates with normal nucleated red blood cell counts, and appropriately grown neonates with normal nucleated red blood cell counts. Analysis of variance, chi(2) tests, and stepwise regression were used for statistical analysis. RESULTS: Two hundred thirty-seven neonates met the inclusion criteria. Forty-three were small for gestational age. Small-for-gestational-age neonates with high nucleated red blood cell counts had significantly lower umbilical artery pH and were more likely to require mechanical ventilation or blood pressure support agents. Subgroup analysis demonstrated that small-for-gestational-age neonates with elevated nucleated red blood cell counts had significantly more adverse outcomes than did small-for-gestational-age neonates with normal nucleated red blood cell counts. Outcomes of small-for-gestational-age neonates with normal nucleated red blood cell counts were essentially identical to those of appropriately grown neonates. CONCLUSION: An elevated nucleated red blood cell count may distinguish the fetus with growth restriction from the small but healthy fetus.

Nucleated red blood cells in growth-restricted fetuses: associations with short-term neonatal outcome.

OBJECTIVE: To determine the utility of the neonatal nucleated red blood cell (NRBC) count as an independent predictor of short-term perinatal outcome in growth-restricted fetuses. METHODS: Hospital charts of neonates with a discharge diagnosis indicating a birth weight <10th percentile were reviewed for perinatal outcome. We studied all eligible neonates who had a complete blood count on the first day of life. After multiple gestations, anomalous fetuses and diabetic pregnancies were excluded; 73 neonates comprised the study group. Statistical analysis included ANOVA, simple and stepwise regression. RESULTS: Elevated NRBC counts were significantly associated with cesarean section for non-reassuring fetal status, neonatal intensive care unit admission and duration of neonatal intensive care unit stay, respiratory distress and intubation, thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhage and neonatal death. Stepwise regression analysis including gestational age at birth, birth weight and NRBC count demonstrated that in growth-restricted fetuses, NRBC count was the strongest predictor of neonatal intraventricular hemorrhage, neonatal respiratory distress and neonatal death. CONCLUSION: An elevated NRBC count independently predicts adverse perinatal outcome in growth-restricted fetuses.

Diagnosis of macrosomia in the postdates population: combining sonographic estimates of fetal weight with glucose challenge testing.

OBJECTIVE: To evaluate the test characteristics of sonographic estimation of fetal weight in the detection of macrosomia in nondiabetic postdates patients as a function of maternal glucose value measured after glucose challenge testing performed at 24-28 weeks of gestation. METHODS: At or beyond 41 weeks' gestation, 656 nondiabetic patients had sonographic estimation of fetal weight. Receiver-operator characteristic curve analysis was used to define the glucose value at which an optimal number of macrosomic fetuses could be identified. The test characteristics of sonography in the prediction of macrosomia in the two populations defined by that cut-off value were evaluated. RESULTS: A glucose level of 120 mg/dL (6.6 mM) was identified as the optimal cutoff for prediction of birth weight > or = 4,000 g. In the group with a glucose level > or = 120 mg/dL, sonographic estimation of fetal weight in the detection of macrosomia offered a sensitivity, specificity, and positive and negative predictive values of 63%, 91%, 71%, and 86%, respectively. In those with glucose level <120 mg/dL, sonography demonstrated a sensitivity, specificity, and positive and negative predictive values of 65%, 89%, 60%, and 91%, respectively. CONCLUSIONS: In postdates nondiabetic patients, routine glucose challenge testing performed early in pregnancy has limited ability to improve the test characteristics of sonography to predict macrosomia. The positive predictive value of sonographically suspected macrosomia increases from 60-71% in patients whose glucose level was > or = 120 mg/dL (P = 0.002).

Receiver operating characteristic curves of ultrasonographic estimates of fetal weight for prediction of fetal growth restriction in prolonged pregnancies.

OBJECTIVE: Recent studies have documented increased perinatal morbidity and mortality rates in the growth-restricted postterm fetus. Our purpose was to evaluate the receiver operating characteristic curve of ultrasonographically estimated fetal weight as a predictor of fetal growth restriction in prolonged pregnancies. STUDY DESIGN: Fetal weight was estimated ultrasonographically within 9 days of delivery (mode 1 day) in members of a cohort of 410 patients with prolonged pregnancies (>41 weeks). Estimated fetal weights were compared with birth weights in receiver operating characteristic curve analysis. RESULTS: The areas under the receiver operating characteristic curves for predicting birth weights <10th percentile (3125 g in this population) and <5th percentile (2930 g in this population) were 0.89 and 0.96, respectively. Both areas were significantly different from an area indicating a useless test. The estimated fetal weight values corresponding to the inflection points for the receiver operating characteristic curves predicting birth weights <10th percentile and <5th percentile were 3370 and 3200 g, respectively. With estimated fetal weight at less than these test cutoff values, the relative risks for a fetus to have a birth weight <10th percentile or <5th percentile were 14.6 (95% confidence interval, 6.25-33.8) and 89.8 (95% confidence interval, 12.1-665), respectively. Analysis of the receiver operating characteristic curves resulted in improved test characteristics relative to using the actual 10th and 5th birth weight percentiles as cutoff values for estimated fetal weight (relative risk of 14.6 vs 9.5 and 89.8 vs 26.0, respectively). CONCLUSIONS: Ultrasonographic estimation of fetal weight is a useful test for predicting fetal growth restriction in prolonged pregnancies. Future studies should evaluate whether intervention on the basis of this identification results in improved perinatal outcome.

Transplantation of CD34 human cells into mice with severe combined immunodeficiency results in functional T cells 4 weeks after transplantation.

OBJECTIVE: Our purpose was to determine whether transplantation of fetal human CD34(+) cells into mice with severe combined immunodeficiency results in functional T cells. STUDY DESIGN: The cells used in this study were isolated from fetal human liver tissue obtained after elective termination of normal 18- to 24-week pregnancies. Women with medical conditions that could confound the outcome were excluded. Cells were labeled with fluorochrome-conjugated antibodies that recognized CD34 or other cell surface antigens. The cells were then sorted with the use of a fluorescein-activated cell sorter. The human sorted cells were injected intraperitoneally in mice with severe combined immunodeficiency. Four groups of mice were studied: group 1, injected with 10(5) CD34(+) cells (n = 17); group 2, injected with 10(5) CD34(-) cells (n = 14); group 3, injected with 10(6) unsorted cells (n = 19); and group 4, sham-injected with phosphate-buffered saline solution as controls (n = 14). At 1, 2, and 4 weeks after transplantation, the peripheral blood monocytes of the study mice were analyzed for functional T cells. Aliquots of cells (10(5)) were incubated for 48 hours with 0, 5, 10, and 20 micrograms of phytohemagglutinin. Thereafter the cells were treated with 1 microCi of tritiated thymidine. Subsequently the incorporation of tritiated thymidine was determined by liquid scintillation counting. RESULTS: Cells from mice transplanted with either unsorted cells, sorted CD34(+) cells, or CD34(-) cells showed a response to phytohemagglutinin that varied with time and with the mitogen concentration. Even though unsorted fetal human liver cells had a maximal response at 2 weeks, this posttransplantation response was not statistically significant. CD34(+) cell response to phytohemagglutinin was significant at 4 weeks after transplantation. CD34(-) cells also had a peripheral blood cell response at 4 weeks after transplantation; however, this response was not statistically significant. In addition, all mice transplanted with fetal human liver cells had some functional T cells at 4 weeks; however, this response was statistically significant only for CD34(+) cells. CONCLUSION: Transplantation of either sorted CD34 (positive or negative) cells or unsorted fetal human liver cell preparations into mice with severe combined immunodeficiency results in functional T cells. However, only the mice with transplanted CD34(+) cells demonstrated a statistically significant response.

Fetal growth restriction at term: myth or reality?

OBJECTIVE: To evaluate the morbidity and mortality associated with the small for gestational age (SGA) fetus born at term to an otherwise uncomplicated pregnancy. METHODS: Small for gestational age, singleton newborns (birth weight below the tenth percentile for gestational age) born at 37-42 weeks' gestation were identified by medical record discharge coding. We excluded gestations complicated by structural or chromosomal abnormalities, maternal diabetes mellitus, preeclampsia, chronic hypertension, asthma, or renal, endocrine, or autoimmune disease. Three low-risk, appropriate for gestational age (AGA) fetuses, matched for gestational age at delivery, were selected randomly for each SGA fetus and served as controls. Maternal and neonatal data were abstracted via medical record review. Statistical analysis included chi2 Fisher exact test, and analysis of variance. RESULTS: There were 67 newborns in the study group and 201 in the control group. There were no fetal or neonatal deaths in any of these cases. The maternal age at delivery, prepregnancy weight, race, smoking status, weight gain during pregnancy, and neonatal gender did not statistically differ between the two groups. Compared with AGA infants, a larger proportion of SGA newborns had low 1-minute Apgar scores and SGA newborns were more likely to be admitted to the neonatal intensive care unit, and have respiratory distress, hypoglycemia, thrombocytopenia, and hyperbilirubinemia. They were also significantly more likely to be delivered by cesarean. CONCLUSION: The SGA newborn from an uncomplicated pregnancy delivered at term has increased neonatal morbidity compared with its AGA counterpart. These results dispute the notion that term growth restriction is a benign condition.

Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies and perinatal outcome.

OBJECTIVE: to assess perinatal outcome in post-term pregnancies in which fetal heart rate (FHR) monitoring revealed either uncomplicated baseline fetal tachycardia (> or = 160 bpm) or fetal bradycardia (< or = 120 bpm). STUDY DESIGN: We performed a case-control study of patients who underwent fetal assessment between July 1989 and June 1995, as part of post-term evaluation. Inclusion criteria consisted of nonlaboring afebrile patients with singleton post-term pregnancies > or = 41 weeks of gestation by strict dating criteria (last menstrual period consistent with ultrasound biometric parameters obtained prior to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat variability were excluded. Baseline FHR was recorded retrospectively by an observer blinded to maternal and neonatal clinical outcome. For each case of uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia (< or = 120 bpm), either two or three control cases (matched for maternal age and parity), with FHR > 120 bpm and < 160 bpm, were identified. Outcome variables assessed included: incidence of cesarean delivery, nuchal cord at delivery, meconium-stained amniotic fluid (AF), 5-min Apgar score < 7, fetal growth restriction (< 10th percentile for 41 weeks' gestation), meconium aspiration syndrome, and neonatal intensive care unit (NICU) admission. Statistical analysis included two-tailed t-test and chi2 test when appropriate, with p < 0.05 considered significant throughout. RESULTS: During the study period 1390 post-term patients (6.81% of the general population) were assessed. Of these, 31 (2.23%) fetuses exhibited baseline FHR > or = 160 bpm, and 76 fetuses (5.46%) exhibited baseline FHR < or = 120 bpm. No significant differences were noted in the incidence of cesarean delivery, presence of nuchal cord at delivery, meconium-stained AF, 5-min Apgar scores < 7, fetal growth restriction, meconium aspiration syndrome, or the incidence of NICU admissions between the groups of patients with fetal tachycardia, bradycardia, and their respective controls. CONCLUSIONS: Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are not associated with an increase in the incidence of adverse perinatal outcome.