Oligohydramnios Sequence

GENESIS

The relative and absolute amount of amniotic fluid tends to decrease during the last trimester as the fetus fills out the uterine cavity, as shown in Fig. 46.1 . A serious deficiency of amniotic fluid will result in significant fetal constraint. Oligohydramnios may be secondary to amniotic rupture and may be accompanied by constrictive, disruptive strands of amnion ( Fig. 46.2 ). The consequences of what has been called very early amnion rupture can include the compressive consequences of early constraint, such as scoliosis and clubfeet, as well as facial clefts, limb-body wall defects, and amniotic bands (see Chapter 49 ). Such early defects can be lethal, resulting in spontaneous abortion. Later rupture of the amnion may or may not be accompanied by amniotic bands, and if bands are present, they are usually limited to constrictive bands around various parts of one or more limbs.

A systematic review and metaanalysis of 15 studies comprising 8067 singleton pregnancies diagnosed with oligohydramnios compared with 27,526 pregnancies with normal amniotic fluid index (AFI) indicated that pregnancies with oligohydramnios had significantly higher rates of an infant with meconium aspiration syndrome, cesarean delivery for fetal distress, admission to the neonatal intensive care unit, and low birth weight. A retrospective study from 2017 to 2019 characterized the degree of oligohydramnios in all low-risk pregnancies at a single institution by AFI (mild = 41–50 mm, moderate = 21–40 mm, and severe = 0–20 mm). Of 610 women, 202 were mild (33.1%), 287 were moderate (47.0%), and 121 were severe (19.8%). Low-risk pregnancies with isolated severe oligohydramnios at term have a higher tendency toward nonreassuring fetal monitoring requiring prompt delivery and adverse neonatal outcomes, thus suggesting a need for close intrapartum surveillance.

Chronic leakage of amniotic fluid for several weeks prior to delivery is one cause of oligohydramnios sequence ( Fig. 46.3 ). In a cohort of 85 women with premature rupture of membranes (PROM; at 14–23.6 weeks’ gestation) the survival rate was 49%. A genetic amniocentesis-related cause of PROM, gestational age at PROM, C-reactive protein >1 mg/dL, and oligohydramnios were significantly associated with fetal survival. Among 49 patients with PROM at 16 to 23 weeks’ gestation from 1998 to 2003, 20 couples out of 49 chose medical termination of pregnancy. Among the remaining 29 continuing pregnancies, the mean delay to delivery after PROM was 2.1 weeks, and the mean gestational age at delivery was 23.2 weeks, with 19 patients delivering after 22 weeks. The main factors predicting fetal survival were the initial AFI (2.9 cm vs. 0.8 cm) and gestational age at delivery (26.7 weeks vs. 22.6 weeks). About 2% of continuing pregnancies were complicated by maternal infection and 83% of the survivors had neonatal respiratory distress syndrome, with 41.2% developing sepsis. There was a uniformly poor prognosis with absent amniotic fluid and PROM before 21 weeks, whereas 63% of infants born after 24 weeks were still alive at 1 week. To evaluate the respiratory and neurologic outcome data at 2 years of age, 15 infants born following PROM prior to 25 weeks with a prolonged latency (14 days) to delivery were compared with an age-matched group of 30 infants. Survivors in this high-risk group (73%) had low morbidity at the time of discharge. Although there was no significant difference in the incidence of bronchopulmonary dysplasia between the groups, the length of hospitalization and respiratory morbidity during the first 2 years of life were significantly higher for infants born following a prolonged period of oligohydramnios, but developmental assessment at 20 to 24 months corrected for gestational age showed no difference between the two groups. A metaanalysis of 43 studies (244,493 fetuses) regarding prediction of amniotic fluid measurements for adverse pregnancy outcome demonstrated a strong association between oligohydramnios and birth weight <10th centile as well as mortality, but despite these strong associations with poor outcome, they did not accurately predict the outcome risk for individuals.

Chronic abruption-oligohydramnios sequence is a clinical condition with prolonged vaginal bleeding and oligohydramnios owing to chronic placental abruption, which results in preterm labor, fetal growth restriction, and neonatal chronic lung disease. The duration of bleeding is a significant predictive factor for poor perinatal/neonatal outcomes, particularly when it begins during the first trimester. Pulmonary hypoplasia in preterm infants in this condition is associated with oligohydramnios and diffuse chorioamniotic hemosiderosis caused by continuing intrauterine hemorrhage owing to chronic placental abuption.

Fetal urination is the major source of amniotic fluid production, and the fetal kidneys begin to function at around 10 to 12 weeks. It is estimated that approximately 1000 to 1200 mL of fetal urine enters the amniotic space each day from the fetal kidneys, with additional fluid entering from the fetal lungs (half of which is swallowed). There is usually a complete turnover of amniotic fluid volume (about 800 mL at term) in less than 24 hours. Roughly 500 mL is swallowed each day (not including swallowed fetal lung fluid), with additional fluid moving into the maternal and fetal circulation through vessels in the amniotic membranes and placenta. By 20 to 25 weeks of gestation fetal urine becomes the major constituent of amniotic fluid; hence oligohydramnios is predominantly a feature of renal or urinary tract malformations during the last half of gestation.

Among 34 cases of prenatal severe bilateral renal hypoplasia, 38% were liveborn and 62% underwent pregnancy termination. Oligohydramnios or anhydramnios was observed in 30 of 34 (88.2%) cases, with normal renal function in 4 of 13 liveborn cases. Overall, 30 of 34 (88.2%) cases had a poor outcome, and serum β ₂ -microglobulin accurately predicted poor renal outcome. Renal oligohydramnios is predominantly caused by congenital abnormalities of the kidney and urogenital tract. Among 36 neonates with renal oligohydramnios treated between 1996 and 2007, the causes included obstructive uropathy (19), polycystic kidney disease (6), renal agenesis/dysplasia (10), and bilateral renal vein thrombosis (1). Overall survival was 58% (21 of 36), and seven patients died within 2 days of birth from respiratory failure, with a low oxygenation index and a diagnosis of renal oligohydramnios before 28 weeks’ gestation predicting poor survival. Among 71 pregnancies with renal oligohydramnios between 2000 and 2008, causes included cystic dysplasia (36), polycystic kidney disease (15), and hydronephrosis (20), with 23 (32%) demonstrating associated anomalies. In 49 fetuses (69%), the diagnosis was made before 24 weeks of gestational age, and 41 of those pregnancies were terminated. Among 25 liveborn neonates, 10 survived and 15 died. Prognostic factors for survival included gestational age at diagnosis (32.2 weeks for survivors vs. 28.1 weeks for nonsurvivors), diagnosis of hydronephrosis (seven in the survivors vs. four in the nonsurvivors), and isolated anomaly (nine in the survivors vs. seven in the nonsurvivors).

Renal pathology is particularly important for genetic counseling. Among 14 cases of fetal or neonatal renal malformations, the results of postmortem examination disclosed renal malformations that were not diagnosed prenatally (86%), provided extensive additional information (50%), or confirmed the diagnosis hypothesis (14%). Renal tubular dysgenesis (RTD) is a severe fetal disorder characterized by the absence or poor development of proximal tubules, early-onset and persistent anuria (leading to oligohydramnios sequence), and ossification defects of the skull. In most cases early death occurs from pulmonary hypoplasia, anuria, and refractory arterial hypotension. RTD may be acquired during fetal development or inherited as an autosomal recessive condition. Inherited RTD is genetically heterogeneous and linked to mutations in the genes encoding the major components of the renin-angiotensin system: angiotensinogen, renin, angiotensin-converting enzyme, or angiotensin II receptor type 1. Mutations result in either the absence of production or lack of efficacy of angiotensin II. Secondary RTD has been observed in various situations, particularly in the donor twin of severe twin-to-twin transfusion syndrome, in fetuses affected with congenital hemochromatosis, or in fetuses exposed to renin-angiotensin system blockers. All causes result in renal hypoperfusion. These examples illustrate the importance of a functional renin-angiotensin system in the maintenance of blood pressure and renal blood flow during fetal life. The pathologic diagnosis of RTD in an anuric fetus with normal renal sonography can be very important for the management of the fetus or neonate. A retrospective study of chromosomal microarray and exome sequencing in 126 fetuses with oligohydramnios revealed pathogenic or likely pathogenic copy number variants in 2 of 124 fetuses. Exome sequencing revealed pathogenic or likely pathogenic in 7 of 32 (21.8%), with 6 of 7 (85.7%) fetuses showing an autosomal recessive inheritance pattern and 3 of 7 (42.9%) variants related to the renin-angiotensin-aldosterone system, which are the known genetic causes of autosomal recessive RTD.

Twin-twin transfusion syndrome is a serious condition that complicates 8% to 10% of twin pregnancies with monochorionic diamniotic placentation. Diagnosis requires monochorionic diamniotic placentation and the presence of oligohydramnios in one sac and of polyhydramnios in the other sac. Serial sonographic evaluation should begin around 16 weeks and continue until delivery. More than 75% of cases remain stable or regress without invasive intervention, with perinatal survival of about 86%, but with advanced twin-twin transfusion syndrome there is a perinatal loss rate of 70% to 100%, particularly when it presents before 26 weeks. Oligohydramnios may be a sign of danger in one member of a monozygotic twin pair because of placental vascular shunting. If one twin is transfusing the other, the donor tends to be hypovolemic with reduced renal blood flow, resulting in oligohydramnios.

Fetal immobilization during late gestation owing to oligohydramnios associated with renal agenesis or obstructive uropathy is associated with positional limb abnormalities but is not associated with reduced bone mass, whereas fetal immobilization owing to fetal akinesia sequence results in thin long bones with decreased bone mass, which suggests that muscular stress is a major factor in fetal periosteal bone growth. Oligohydramnios may be a sign of poor placental function and is frequently associated with intrauterine growth retardation, intrapartum asphyxia, and fetal demise, because poor placental function (such as might occur with severe preeclampsia or pregnancy-induced maternal hypertension) leads to decreased fetal hydration, growth retardation, and decreased fetal urinary flow.

FEATURES

Amniotic fluid volume can be determined by ultrasound and may be predictive of some types of fetal and maternal problems, as described previously. Amniotic fluid volume rises progressively from 10 to 20 mL at 10 weeks to 800 mL at 24 weeks and then remains relatively constant at 700 to 800 mL until term (see Fig. 46.1 ). After 40 weeks amniotic fluid volume declines by about 8% per week, reaching 400 mL at 42 weeks. Oligohydramnios (less than fifth percentile for gestational age) is approximately 300 mL. Amniotic fluid volume assessment is usually determined by ultrasound after 16 weeks to monitor patients with preterm PROMs. Mechanisms for recirculation of amniotic fluid include fetal breathing lung movements, swallowing, absorption through the fetal gastrointestinal tract, and excretion through fetal urine production. Oligohydramnios requires evaluation for fetal growth restriction and genitourinary issues, such as renal agenesis, multicystic dysplastic kidneys, RTD, ureteropelvic junction obstruction, and bladder outlet obstruction. Premature preterm rupture of membranes should also be considered as a cause of oligohydramnios.

Persistent oligohydramnios may be an indication for prompt delivery, and antepartum testing with nonstress tests and fetal biophysical profiles can facilitate this decision. Perinatal mortality is increased when sonographic determination of amniotic fluid volume is marginal, and it is increased even more with severe oligohydramnios. A prospective study of 180 pregnant women at 37 to 40 weeks of gestation compared women with a mean AFI of 4.14 cm (AFI ≤fifth percentile) with a control group (mean AFI = 10.14 cm). In the control group 53% of patients were induced for reasons other than oligohydramnios, whereas in the study group 86% of patients were induced for oligohydramnios, with 65% of patients in the study group and 24% in the control group demonstrating a nonreactive nonstress test. Among the control group, 33% had a cesarean section, whereas 67% delivered vaginally. In the study group, 34% delivered vaginally and 66% had a cesarean section. The 5-minute Apgar score was <7 in 34% of the study group and 11% of the control group, and 33% neonates in the control group and 64% in the study group had birth weights <2.5 kg. A metaanalysis of 43 studies (244,493 fetuses) demonstrated a strong association between oligohydramnios, low birth weight, and perinatal mortality. A second systematic review and metaanalysis used 12 studies and compared 2414 pregnancies with isolated oligohydramnios with 35,585 pregnancies with normal AFI and found oligohydramnios at term was associated with significantly higher rates of labor induction, cesarean sections, and short-term neonatal morbidity.

The features of oligohydramnios sequence often include those of breech deformation sequence, because about 50% of infants experiencing oligohydramnios are in breech presentation at birth due to their inability to undergo normal version in late gestation. The term oligohydramnios tetrad describes the primary features in nonrenal cases: facial compression (flattened nose with enlarged, flattened ears), aberrant hand and foot positioning, fetal growth deficiency, and pulmonary hypoplasia ( Fig. 46.4 ).

Craniofacial

The head usually looks as though a silk stocking has been pulled down over it, causing a flattened nose and the appearance of low-set, flattened, enlarged external auricles ( Fig. 46.5 ).