Postdates and antenatal testing

The standard definition of a prolonged pregnancy is 42 completed weeks of gestation. The incidence of prolonged pregnancy varies depending on the criteria used to define gestational age at birth. It is estimated that 4 to 19% of pregnancies reach or exceed 42 weeks gestation. Several studies that have used very large computerized databases of well-dated pregnancies provided insights into the incidence and nature of adverse perinatal outcome such as an increased fetal and neonatal mortality as well as increased fetal and maternal morbidity in prolonged pregnancy. Fetal surveillance may be used in an attempt to observe the prolonged pregnancy while awaiting the onset of spontaneous labor. This article reviews the different methodologies and protocols for fetal surveillance in prolonged pregnancies. On the one hand, false-positive tests commonly lead to unnecessary interventions that are potentially hazardous to the gravida. On the other hand, to date, no program of fetal testing has been shown to completely eliminate the risk of stillbirth.     

Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges

OBJECTIVE: To estimate a normal reference range for thyroid-stimulating hormone (TSH) at each point in gestation in singleton and twin pregnancies. METHODS: All women enrolling for prenatal care from December 2000 through November 2001 underwent prospective TSH screening at their first visit. Separate nomograms were constructed for singleton and twin pregnancies using regression analysis. Values were converted to multiples of the median (MoM) for singleton pregnancies at each week of gestation. RESULTS: Thyroid-stimulating hormone was evaluated in 13,599 singleton and 132 twin pregnancies. Thyroid-stimulating hormone decreased significantly during the first trimester, and the decrease was greater in twins (both P < .001). Had a nonpregnant reference (0.4-4.0 mU/L) been used rather than our nomogram, 28% of 342 singletons with TSH greater than 2 standard deviations above the mean would not have been identified. For singleton first-trimester pregnancies, the approximate upper limit of normal TSH was 4.0 MoM, and for twins, 3.5 MoM. Thereafter, the approximate upper limit was 2.5 MoM for singleton and twin pregnancies. CONCLUSION: If thyroid testing is performed during pregnancy, nomograms that adjust for fetal number and gestational age may greatly improve disease detection. Values expressed as multiples of the median may facilitate comparisons across different laboratories and populations.     

Antenatal fetal assessment: multifetal gestation--an overview

As prevalence of multifetal gestation has increased in the United States, antenatal surveillance of these pregnancies has gained importance. This article focuses on the assessment of twin pregnancy, since critical data are lacking for the surveillance of higher order multiple gestations. Twin pregnancies encounter risks that differ in nature, frequency, and intensity from those seen in singleton pregnancies. Most of these risks stem from subnormal or discordant fetal growth or abnormalities of placentation. Sonographic modalities play key roles in antepartum surveillance. These include fetal biometry, serial growth studies, amniotic fluid volume assessment, Doppler velocimetry of fetal-placental circulation, and biophysical profile testing. Fetal heart rate testing, specifically nonstress testing, has also been used extensively in twin surveillance. This article examines the specific application of these modalities to twin gestation and reviews the best evidence available for their support. Assessment of unique risk conditions of twin-twin transfusion, monoamniotic twinning, and intrauterine death of one twin is addressed. Based on current data, a strategic outline for assessment of twin pregnancy is presented.     

Postdate fetal surveillance: is 41 weeks too early?

During an 18-month period, 293 patients had a nonstress test and ultrasonographic evaluation of amniotic fluid volume twice weekly beginning at 41 weeks' gestation. Patients were admitted for induction of labor for either an abnormal nonstress test result or oligohydramnios. A control population consisted of 59 low-risk patients who were delivered between 39 and 41 weeks' gestation and had antepartum testing within 4 days of delivery. Study patients who were delivered between 41 and 42 weeks' gestation had a significantly increased incidence of abnormal nonstress tests, oligohydramnios, cesarean sections for fetal distress, and admissions to the neonatal intensive care unit compared with control patients. The abnormal fetal testing and adverse perinatal outcome associated with pregnancies over 42 weeks were also found in pregnancies between 41 and 42 weeks' gestation. These data support the concept that postdate fetal testing should begin at 41 weeks of gestation.     

Pre-existing type I and type II diabetes in pregnancy

Women with pre-gestational diabetes are high-risk pregnancies. Hyperglycaemic is toxic to the developing fetus and is associated with a higher incidence of congenital malformation, miscarriage, macrosomia and stillbirth. Complications can be reduced with tight glycaemic control, and management should ideally start pre-conceptually. During pregnancy a woman’s insulin requirements change and those managed pre-pregnancy on diet or oral medication may need to start insulin. Pre-gestational diabetics require close maternal and fetal monitoring, including screening for the progression of maternal diabetic complications such as retinopathy and nephropathy, and fetal growth scans. Their pregnancies are complex and a multidisciplinary approach should be used. In this article we will discuss the background physiology, the effect of pregnancy on diabetes, the potential fetal and maternal complications, and how these can be minimized by intensive management from pre-conception to the post-natal period, including the contribution of recent studies and guidelines.     

Perinatal outcome in the diabetic pregnancy: a retrospective analysis

A retrospective analysis was done of all pregnancies in class B through R diabetics over a two-and-one-half-year period. This study demonstrates that early hospitalization, assessment of fetal status via estriols and oxytocin challenge test, fetal maturity studies, close medical supervision of the diabetes problem and advances in neonatology have combined to significantly reduce perinatal morbidity and mortality. The expense of prolonged maternal hospitalization is justified by the savings in newborn and child care, which would otherwise be increased. This approach can be used in any obstetric center. The philosophic question is discussed of the increased incidence of congenital malformations and diabetes in offspring of diabetic mothers.     

Fetal surveillance in the pregnancy complicated by diabetes mellitus

During the last decade, outpatient protocols have been developed for antepartum fetal assessment in pregnancies complicated by diabetes mellitus. This approach has been associated with a markedly reduced cost of health care and emotional stress for patients and their families attributable to lengthy hospitalization. These programs have used primarily biophysical testing, with twice weekly NSTs followed by a CST or biophysical profile when necessary. Most recently, Doppler studies have been investigated as a method for identifying fetal compromise. Maternal assessment of fetal activity can be used as a screening test in most surveillance programs. Essential to the success of these protocols has been our ability to monitor maternal glycemia and to maintain glucose levels in the physiologic range through aggressive therapy with insulin and diet. Reassuring tests of fetal condition are present in most diabetic women and therefore permit fetal maturation to take place before delivery.     

Fetal behavioural states and hypertensive pregnancy.

Delay in fetal maturation in diabetic and accelerated fetal maturation in hypertensive pregnancies have been reported in the past. The spontaneous activity of fetal nervous system during pregnancy was followed longitudinally in a group of 29 normal pregnancies from 28 x th to 40 x th week of gestation by means of fetal behavioural states determination. 1 F state (quiet sleep) progressively increases from median values of 5.0% to values of 22.5-25% at term of pregnancy. This state represents the positive activity of inhibitory centers has been related to a positive evolutionary process of brain maturation according to preceding experiences conducted on experimental models and preterm babies followed with EEG and direct observation in the early neonatal period. The method of behavioural states determination has been applied to a group of 33 gestational diabetes (GDM) pregnant women followed longitudinally, and a clear reduction of development of 1 F state has been evidentiated, with significant differences (p less than 0.001) at 35-36 weeks of gestation versus the control group. The normal values are reached in concomitance with L/S value of maturity. In 30 pregnant women affected by gestational hypertension (GH) different result are obtained: 1 F state seems to develop earlier, and is increased (p less than 0.001) around 30-32 weeks versus the control group if a fetal growth reduction is present. The value of 1 F behavioural state in the evaluation of fetal condition of pathological pregnancies is discussed.     

Fetal renal tubular function during late pregnancy and diabetes mellitus.

The effect, if any, of diabetes mellitus on the fetal renal tubule has not been previously studied. The concentration of beta2 microglobulin in amniotic fluid is a marker of fetal renal tubular function and normally decreases with advancing gestation, implying increasing tubular function. This relationship was found to be disrupted in 12 diabetic pregnancies, suggesting that the fetal renal tubular cell may represent an example of altered fetal functional maturation occurring during diabetic pregnancy.     

Non-invasive first trimester determination of fetal gender: a new approach for prenatal diagnosis of haemophilia

Ten carriers of haemophilia referred for prenatal diagnosis were offered first trimester non-invasive fetal gender determination by ultrasound and analysis of free fetal DNA (ffDNA) in maternal plasma in an attempt to reduce the need for an invasive diagnostic procedure in female pregnancies. Although repeat testing was required in three cases, fetal gender was determined correctly in all cases (four females, six males) at a median gestation of 12(+3) (11(+2) to 14(+1)) using both methods. In all cases of a female fetus, the mothers opted not to have invasive testing. Both methods provide a reliable option of avoiding invasive testing in female pregnancies.     

Assessment of uteroplacental circulation with radioisotopes

The authors have evaluated placental blood flow using a non-invasive radioisotopic approach, with the intravenous administration of 1 mCi 113mIn. The method is evaluated in 20 normal pregnancies, in 24 patients with intrauterine growth retardation, in 8 patients with iso-Rh-immunization and in 9 patients with gestational diabetes. In the group with intrauterine growth retardation 2 pregnancies with extensive fetal malformations were included. In one case without evident histological placental alteration the index was 3.94 at 34 weeks of gestation and 5.62 at 36 weeks of gestation. In the second one with placental infarcts the index was 3.46 at 38 weeks of gestation. Normal pregnancies showed a flow index of 5.50 +/- 1.57 (1 s.d.) units compared to the pathological pregnancies value of 2.74 +/- 0.90 (1 s.d.) units. (p less than 0.001). The conclusions drawn are: The method is very well suited to clinical evaluation of placental blood flow. The evaluation of placental blood flow cannot be directly equated with fetal development as it is not its only determinant. This method is a indirect index of placental function in small for gestational age fetuses with malformations.     

Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus

Fourteen placentas from pregnancies complicated by insulin-dependent diabetes mellitus have been examined by quantitative morphometry. The results have been compared with those from 22 placentas of comparable gestation from uncomplicated pregnancies. The volume of parenchymatous tissue in the placentas from diabetic mothers was significantly increased while the volume of nonparenchyma was decreased. The villous surface area was increased in placentas from the diabetic group, the mean value being 17.3 m2 compared with the 11.4 m2 of the normal group. This increase was larger than would be expected when the increase in fetal weight of some babies born to diabetic mothers is taken into account.     

Gestation sac size in in-vitro fertilization pregnancies

The gestation sac size in pregnancies resulting from in-vitro fertilization (IVF) and embryo transfer have been compared with those in spontaneous pregnancies. Small-for-dates gestational sac sizes were found in 36% of the IVF pregnancies. This proportion held for both singleton and multiple pregnancies. With increasing gestation beyond 8 weeks the gestation sac volume increasingly approached normal. In contrast to spontaneous conceptions, IVF pregnancies had a low rate of pregnancy loss once fetal heart movements were demonstrated, when the gestation sac size was small-for-dates. Small sac size in an IVF pregnancy may lead to the misdiagnosis of a failed pregnancy.     

Maternal and perinatal outcomes in women with gestational diabetes mellitus as compared to nondiabetic controls.

OBJECTIVE: To determine maternal and fetal outcomes in pregnancies complicated by gestational diabetes mellitus as compared to nondiabetic pregnancies matched on the basis of age and parity and to study the association between different treatment regimens and fetal outcomes. STUDY DESIGN: The records of 128 consecutive pregnancies complicated with gestational diabetes mellitus and 138 nondiabetic controls matched on the basis of age and parity were studied. Patients with gestational diabetes mellitus were treated either with diet only or diet in combination with insulin. Data were collected from medical records of the patients and birth records of the newborns. RESULTS: Despite treatment, the gestational diabetes mellitus group had a significantly higher frequency of cesarean section, preterm delivery and admission to a neonatal unit (P < .05). Preterm delivery and admission to a neonatal unit were significantly higher in the gestational diabetics treated with diet plus insulin as compared to the diet-only group (P < .05). CONCLUSION: Pregnancies complicated by gestational diabetes mellitus are associated with a higher frequency of adverse maternal and fetal outcomes, and adverse outcomes seems to be more frequent in patients treated with diet plus insulin.     

Novel placental ultrasound assessment: Potential role in pre-gestational diabetic pregnancy

Objectives

Management of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics.

Methods

This was a prospective cohort study of 50 women with diabetes and 250 controls (12–40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology.

Results

Placental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found.

Conclusions

This study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.     

Gestation sac size in in-vitro fertilization pregnancies

Summary. The gestation sac size in pregnancies resulting from in-vitro fertilization (IVF) and embryo transfer have been compared with those in spontaneous pregnancies. Small-for-dates gestational sac sizes were found in 36% of the IVF pregnancies. This proportion held for both singleton and multiple pregnancies. With increasing gestation beyond 8 weeks the gestation sac volume increasingly approached normal. In contrast to spontaneous conceptions, IVF pregnancies had a low rate of pregnancy loss once fetal heart movements were demonstrated, when the gestation sac size was small-for-dates. Small sac size in an IVF pregnancy may lead to the misdiagnosis of a failed pregnancy.     

Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation

Placentas from pregnancies complicated by pre-eclampsia, essential hypertension, hypertension complicated by pre-eclampsia and from normotensive pregnancies resulting in the birth of a singleton small-for-dates (SFD) infant have been studied by quantitative morphometry. The findings have been compared with those from placentas of uncomplicated pregnancies. The placentas from pregnancies complicated by pre-eclampsia and those resulting in a SFD baby had a significantly lower total volume, volume of parenchyma and villous surface area when compared with normal pregnancies of comparable gestation. They also had an increase in areas of multiple infarction and in the volume proportions occupied by fetal capillaries. The placentas from women with essential hypertension uncomplicated by pre-eclampsia were as large as those from normal pregnancies and the villous surface areas were as high. Villous surface area measurements in the different groups were related to gestation and to fetal weight.     

Significance of amniotic fluid glucose in pregnancy

Amniotic fluid glucose values were measured in 285 women with normal and abnormal pregnancies. A progressive decrease in glucose values was observed with advancing gestation. Complications in pregnancy did not influence the amniotic fluid glucose value for the given gestational age. In patients with diabetes, very high levels were found, but these progressively decreased with advancing gestation. Since abnormal conditions in pregnancy, other than diabetes, do not affect the amniotic fluid glucose level, it seems to be a reliable tool in assessing fetal maturity. Values above 15 mg/100 ml rule out term pregnancies and those below 5 mg/100 ml, prematurity.     

Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation

Summary. Placentas from pregnancies complicated by pre-eclampsia, essential hypertension, hypertension complicated by pre-eclampsia and from normotensive pregnancies resulting in the birth of a singleton small-for-dates (SFD) infant have been studied by quantitative mor-phometry. The findings have been compared with those from placentas of uncomplicated pregnancies. The placentas from pregnancies compli-cated by pre-eclampsia and those resulting in a SFD baby had a signifi-cantly lower total volume, volume of parenchyma and villous surface area when compared with normal pregnancies of comparable gestation. They also had an increase in areas of multiple infarction and in the volume proportions occupied by fetal capillaries. The placentas from women with essential hypertension uncomplicated by pre-eclampsia were as large as those from normal pregnancies and the villous surface areas were as high. Villous surface arca measurements in the different groups were related to gestation and to fetal weight.     

Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus

Summary. Fourteen placentas from pregnancies complicated by insulin-dependent diabetes mellitus have been examined by quantitative morphometry. The results have been compared with those from 22 placentas of comparable gestation from uncomplicated pregnancies. The volume of parenchymatous tissue in the placentas from diabetic mothers was significantly increased while the volume of non-parenchyma was decreased. The villous surface area was increased in placentas from the diabetic group, the mean value being 17·3 m² compared with the 11·4 m²of the normal group. This increase was larger than would be expected when the increase in fetal weight of some babies born to diabetic mothers is taken into account.