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Keywords:

  • Absence of diastolic flow;
  • fetal previability;
  • umbilical artery Doppler

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Objective

To evaluate the outcome of pregnancies complicated by placental insufficiency and abnormal umbilical artery Doppler prior to viability.

Design

A retrospective cohort study.

Setting

Italy.

Population

Singleton pregnancies with fetal growth restriction and absence of end-diastolic velocities (AEDVs) in the umbilical arteries prior to 24 weeks.

Methods

A retrospective cohort study of singleton pregnancies with fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks.

Main outcome measures

Fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks.

Results

Of 16 fetuses first seen at 20–23 weeks, only 12 survived and one of these developed cerebral palsy. Severe hypertensive disorders occurred in three mothers. In four women, the Doppler waveforms progressively improved and developed a normal pulsatility. These fetuses had a better outcome than those that had persistent alterations: they were delivered later (34 versus 28 weeks), had a larger birthweight (1598 versus 630 g) and developed fewer complications.

Conclusions

Placental insufficiency with AEDV in the umbilical arteries prior to fetal viability is associated with a high probability of perinatal death and neonatal complications. However, progressive amelioration of Doppler indices occurs in a subset of women, and these fetuses have a much better outcome.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Placental insufficiency encompasses a wide spectrum of severity. Fetal growth restriction with absence of end-diastolic velocities (AEDVs) in the Doppler waveforms of the umbilical artery is a well-established entity associated with an excess of adverse outcomes, including perinatal death, severe morbidity and long-term neurological compromise.[1, 2]

In most women, the Doppler abnormality is recognised in the third trimester. There is limited experience with cases identified prior to viability, which presumably correspond to the most severe end of the clinical spectrum.[1] The aim of our study was to evaluate the outcome of pregnancies seen in our centre to obtain information useful for counselling and clinical management.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

This is a retrospective cohort study of pregnancies with severe placental insufficiency and AEDV in the umbilical arteries prior to fetal viability. The inclusion criteria were as follows: singleton pregnancy; gestational age at diagnosis, 20–23 weeks; estimated fetal weight and/or abdominal circumference, less than fifth centile[3]; normal fetal anatomy; AEDV in both umbilical arteries. Antenatal assessment included fetal biometry, amniotic fluid volume, Doppler velocimetry of the umbilical arteries, uterine arteries and ductus venosus (DV), and computerised cardiotocography (cCTG). Gestational age was always confirmed by first-trimester biometry. Doppler examinations were performed as described previously[4-6]: ultrasound 3.5–5-MHz convex probes were used, the high-pass filter was set at 100 Hz or lower, the insonation angle was <30° and the sample volume was adjusted to cover the entire vessel. Both umbilical arteries were sampled close to the placental insertion. AEDV was diagnosed only when the alteration was persistent throughout the entire examination. The uterine artery was examined close to the crossing with the external iliac artery and the waveforms were considered to be abnormal when the mean resistance index was greater than the 95th centile with or without bilateral notches. The DV waveforms were considered to be abnormal when either the pulsatility index was greater than the 95th centile and/or velocities were absent or reversed during atrial systole.

After the initial diagnosis, sonograms were performed on a daily basis. The umbilical artery and DV were assessed at every examination. Uterine arteries were examined every 1–2 weeks. cCGT was performed on a daily basis from 25 weeks of gestation and was considered not to be reassuring in the presence of a short-term variability of <3.5 ms,[7] or with repetitive decelerations. In those women in whom umbilical artery Doppler improved, the frequency of fetal examinations was decreased to one to three times per week until delivery.

A detailed follow-up was obtained in each case. Infants were considered to be small for dates when the birthweight was less than the 10th centile, according to Italian charts used in our hospital.[8]

Results are presented as the median (range) for continuous variables and as percentages for categorical variables. Continuous and categorical variables were compared using Wilcoxon and Fisher exact tests, respectively. Statistical significance was defined as P < 0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Over a 3-year period, 16 singleton pregnancies in the second trimester with AEDV in the umbilical arteries, presumably as a consequence of uteroplacental insufficiency, were seen. The median gestational age at diagnosis was 22 + 3 weeks (range, 20 + 0 to 23 + 3 weeks) and the median estimated fetal weight was 324 g (range, 248–509 g). The maternal characteristics of the study population are reported in Table 1. Three women had chronic hypertension, two had a history of gestational hypertension and two had been diagnosed previously with thrombophilias. In one woman with HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome, the pregnancy was terminated at 20 weeks.

Table 1. Clinical data of pregnant women
 Transient AEDV (n = 4)Persistent AEDV (n = 12) P
  1. a

    Lupus anticoagulant activity (LAC), heterozygous MTHFR mutation.

Maternal age (years), median (range)37 (25–42)34 (31–43)0.74
Primigravidas 2 80.55
Smokers 1 31.0
Thrombophiliasa 0 20.38
Chronic hypertension 0 30.26
Previous hypertensive disorders in pregnancy 0 20.38
Previous intrauterine growth restriction 0 20.38

In 11 women, Doppler ultrasound documented AEDV in both umbilical arteries until delivery. In the remaining four women, a progressive amelioration was noted throughout pregnancy. After a median period of 3 weeks (range, 2–4 weeks) with uninterrupted AEDV, diastolic velocities appeared. The pulsatility index was initially >95th centile, but returned within the normal range in all women within 27 weeks of gestation. The sonographic findings at the time of diagnosis are reported in Table 2. Oligohydramnios was present in two women, both in the persistent AEDV group. DV velocimetry was available in 11 women and the pulsatility index for vein was >95th centile in two women, one in the group with transient AEDV and one in the group with persistent AEDV.

Table 2. Ultrasound findings at the time of diagnosis
 Transient AEDV (n = 4)Persistent AEDV (n = 12) P
Fetal estimated weight (g), median (range)309 (255–509)324 (248–448)0.50
Uterine artery resistance index, median (range)0.69 (0.61–0.84)0.71 (0.55–0.88)0.50
Oligohydramnios020.38
Ductus venosus pulsatility index >95th centile110.76

In 14 women, Doppler waveforms of the uterine arteries demonstrated increased pulsatility, with a mean resistance index (RI) >95th centile and bilateral notches in all cases. The median RIs were 0.69 (range, 0.61–0.84) and 0.73 (range, 0.40–0.88) in the transient AEDV and AEDV groups, respectively (P = 0.5).

A summary of the main clinical data of the pregnancies is reported in Table 3. Three women in the persistent AEDV group developed hypertensive disorders (severe pre-eclampsia in two, HELLP syndrome in one). Excluding the woman who opted for pregnancy termination, the median gestational age at delivery was 29 weeks (range, 24–36 weeks). Women with persistent and transient AEDV were delivered at 28 weeks (range, 24–30 weeks) and 34 weeks (range, 30–36 weeks), respectively. A caesarean section was performed in 14 women. The indications included arrested fetal growth in eight women, abnormal DV waveforms in two (in both cases, delivery occurred within 24 hours from the detection of the abnormal finding), nonreassuring cCTG in one, severe pre-eclampsia in two and preterm premature rupture of the membranes in one. There was only one vaginal delivery, following the induction of labour of a multiparous woman at 36 weeks. The neonate had a birthweight of 1750 g and did well.

Table 3. Pregnancy and neonatal outcomes
 Transient AEDV (n = 4)Persistent AEDV (n = 11) P
  1. HELLP, haemolysis, elevated liver enzymes and low platelet count; NICU, neonatal intensive care unit.

  2. a

    Excluding one woman with termination of pregnancy.

  3. b

    At least one of the following: bronchopulmonary dysplasia, necrotising enterocolitis, periventricular leucomalacia, intraventricular haemorrhage grade >2, retinopathy.

Preeclampsia or HELLP syndrome 0 30.26
Gestational age at delivery (weeks), median (range)* 34 (30–36) 28 (24–30)0.002
Birthweight (g), median (range)*1598 (1100–1750)630 (408–951)0.0001
Placental weight at delivery (g) 400 (350–440)200 (170–400)0.0001
Arterial pH, median (range)* 7.33 (7.308–7.465) 7.269 (7.19–7.382)0.20
NICU admission* 3 110.08
Need for ventilation* 3 110.08
Surfactant use* 0 70.02
Severe neonatal morbidity** 0 60.06

All but one of the infants was small for gestational age. The median z-score of birthweight was −1.53 (range, −4.62 to 2.25), and there was no significant difference between the transient and persistent AEDV groups.

There were three neonatal deaths among the 15 infants who were delivered alive, all with a birthweight of <600 g. The median time of neonatal follow-up was 30 months (range, 24–58 months). Periventricular leucomalacia was diagnosed in one infant born at 28 weeks of gestation with a birthweight of 631 g. At the time of writing, this infant is 3 years of age and is affected by cerebral palsy. This was the only case with severe neurological symptoms in our series.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References

Our results confirm that a small fetus with AEDV at 20–23 weeks of gestation has a significant risk of perinatal death and complications. In our series, intact survival occurred in about two-thirds of cases. Severe maternal hypertensive disorders were seen in three women. However, in four of the 15 women, the Doppler waveforms of the umbilical arteries improved throughout gestation and eventually became normal. Although significant growth restriction was also present in these women, fetuses were delivered much later in gestation, had a larger birthweight and developed less complications compared with those that had persistent Doppler abnormalities.

The underlying pathophysiology remains uncertain. Under normal conditions, the umbilical circulation develops low impedance from the early second trimester. In severe placental insufficiency, increased pulsatility of the umbilical arteries is thought to derive from poor growth of the placental villi and/or secondary occlusion of the placental fetal vessels.[9-12] Usually, when AEDV is established in such a context, Doppler velocimetry remains stable or tends to worsen.[12, 13] Our results suggest that, at least in some cases identified around midgestation, the Doppler abnormalities disappear later on, usually by 27 weeks, and in these cases a much better outcome is observed. Unfortunately, our retrospective review did not identify any clear findings useful to differentiate these cases prospectively. A correlation was noted between persistent AEDV and maternal hypertension, abnormal obstetric history and midtrimester oligohydramnios. However, sonographic findings at the time of initial diagnosis were similar in the two groups.

We acknowledge that the retrospective design and small sample size limit the value of our results. However, we are unaware of any similar study.

In conclusion, placental insufficiency with abnormal umbilical artery velocimetry in the second trimester is associated with a significant risk of fetal death and complications, and of potentially severe maternal complications. However, a subset of women will demonstrate progressive amelioration of the Doppler indices, and their fetuses will have a much better outcome. At present, there are no clear clues to differentiate between these two groups.

Disclosure of interests

The authors report no disclosure of interests.

Contribution to authorship

GS designed the study and reviewed the data. AC and LC collected the data and performed statistical analyses. All authors contributed to the interpretation of the data and the writing of the manuscript.

Details of ethics approval

The study was carried out following the ethical rules of St. Orsola-Malpighi General Hospital, Bologna, Italy. Reference number: 44/2011/1/Omb. Date of approval: 12 July 2011.

Funding

The authors report no funding.

Acknowledgements

The authors report no acknowledgements.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References