Hans A. Zondervan

Risk factors for preeclampsia in nulliparous women in distinct ethnic groups: a prospective cohort study☆

Objective To determine whether baseline characteristics during early pregnancy, proposed as potential risk factors for preeclampsia, show differences in prevalence and effects within distinct ethnic groups. Methods In a prospective cohort study of 2413 healthy nulliparous women from eight midwives practices, we analyzed risk factors for preeclampsia (maternal age, body mass index, blood pressure at booking, smoking habit, and abortion history) in white, Mediterranean, Asian, and black women. In a univariate analysis, we estimated the relative risk of preeclampsia for the baseline variables and for ethnicity. In a multivariate analysis, we evaluated the simultaneous effect of the baseline variables in white (n = 1641) and black (n = 317) women. Results Significant differences were found in the prevalence of the risk factors in different ethnic groups. In the univariate analysis, the relative risk (RR) of preeclampsia in black women was 2.4 (95% confidence interval [CI] 1.1, 5.6) compared with white women. In the multivariate analysis in white women, the adjusted RR of preeclampsia for a diastolic blood pressure at booking above 70 mmHg was 4.4 (CI 0.9, 20.8). Among black women, the adjusted RR of preeclampsia was increased for high maternal age (RR 1.2; CI 1.0, 1.4), but not for a diastolic blood pressure at booking above 70 mmHg (RR 0.8; CI 0.2, 3.9) Conclusion In studies of risk factors for preeclampsia, black women should be analyzed separately from white women.

The “brain-sparing” effect: Antenatal cerebral Doppler findings in relation to neurologic outcome in very preterm infants

OBJECTIVEnOur purpose was to study the relationship between fetal cerebral circulation and neurologic outcome.nnnSTUDY DESIGNnIn 117 high-risk fetuses (gestational age 25 to 33 weeks) flow velocity waveforms were recorded from the umbilical and medial cerebral arteries. The ratio between umbilical and cerebral pulsatility indexes was calculated. A ratio above a predefined tolerance limit was used as an index for the brain-sparing effect. Neonatal neurosonography and neurologic examination were used as outcome parameters.nnnRESULTSnAntenatally raised ratios are associated with poor obstetric outcome (fetal death and fetal growth retardation). The incidence of intracranial hemorrhages and ischemic lesions was not different for infants with a normal or raised prenatal ratio. The incidence of neurologic abnormalities was the same for both ratio groups.nnnCONCLUSIONSnThe brain-sparing effect is a mechanism to prevent fetal brain hypoxia rather than a sign of impending brain damage.

Neurodevelopmental outcome at three years of age after fetal 'brain-sparing'

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal brain-sparing in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.

Intra‐observer and inter‐observer reliability of the pulsatility index calculated from pulsed Doppler flow velocity waveforms in three fetal vessels

Objective Study of the intra observer and inter observer reliability of the pulsatility index, calculated from pulsed Doppler recordings of three fetal vessels.

Intensification of fetal and maternal surveillance in pregnant women with hypertensive disorders

Objective: To examine the need to intensify fetal and maternal surveillance in pregnant women with mild pregnancy hypertension. Methods: The multi‐center cohort study in 2413 healthy nulliparae analyzed differences in hypertension‐related adverse events (small‐for‐gestational age, perinatal mortality, eclampsia, abruptio placentae and HELLP syndrome) according to maximum diastolic blood pressure and proteinuria. Results: Compared to the reference group (diastolic blood pressure 70–85 mmHg) (n=1882) the relative risks of adverse fetal and maternal outcome in 34 proteinuric hypertensive women were 8.9 (95% CI 3.3–24.1) and 41.5 (95% CI 9.7–178.4), respectively. In 203 non‐proteinuric women with a maximum diastolic blood pressure of ≥95 mmHg only the relative risk of adverse maternal outcome was increased (11.6, 95% CI 3.1–42.8), but it was not increased in 230 non‐proteinuric women with a maximum diastolic of 90 mmHg. Conclusions: Intensified surveillance in women with mild pregnancy hypertension is not indicated and should be reserved for groups with increased fetal and maternal risk.

Fetal brain sparing is associated with accelerated shortening of visual evoked potential latencies during early infancy

OBJECTIVEnOur purpose was to assess the effects that fetal growth restriction exerts on the myelination of the developing brain.nnnSTUDY DESIGNnFetal haemodynamic centralization, an adaptive strategy to growth restriction caused by placental insufficiency, was determined by Doppler ultrasonography. Infants with a raised ratio between umbilical artery pulsatility index and cerebral artery pulsatility index are severely growth restricted. Visual evoked potentials give information on the degree of brain myelination. Shortening of visual evoked potential latencies is a normal feature of myelination. In a consecutive series of 105 Neonates, visual evoked potentials were recorded at the corrected ages of 6 months and 1 years. Correction for possible confounders, such as cranial ultrasonographic findings, gestational age, and head circumference, was performed.nnnRESULTSnAt 6 months, infants with a raised umbilical artery/cerebral artery pulsatility index ratio have shorter visual evoked potential latencies. Opposite of neonates with a normal umbilical artery/cerebral artery ratio, they show no postnatal maturational shortening of visual evoked potential latencies.nnnCONCLUSIONnAccelerated neurophysiologic maturation, found in infants with a high umbilical artery/cerebral artery ratio, might be the result of a beneficial adaptive process to severe fetal growth restriction.

Low sodium diet and pregnancy‐induced hypertension: a multi‐centre randomised controlled trial

Objective To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy‐induced hypertension.

The influence of maternal whole blood viscosity on fetal growth

To explore the relevance of the rheological properties of maternal blood in pregnancy to fetal growth a study of whole blood viscosity (WBV) was conducted in the early third trimester of 138 pregnancies. A significant negative correlation was found between WBV at low shear rate and birthweight centile. As the rheological parameters were found to be negatively correlated with the placenta coefficient, an independent role for maternal WBV seems likely. When WBV, placental weight and degree of infarction accounted for significant contributions in a logistic regression model, diastolic blood pressure data did not assist in the correct prediction of occurrence of a low birthweight centile (less than 10th). A simplified model is proposed, to explain the mechanisms by which some clinical variables may express their influence on fetal growth. In conclusion, it is suggested that WBV might be considered one of the factors which determine the efficacy of placental perfusion on the maternal side. However, as this variation in efficacy of placental perfusion is only weakly reflected in variations in birthweight, the influence of WBV on fetal growth cannot be very important.

Effect of fetal brainsparing on the early neonatal cerebral circulation.

The effect of antenatal brainsparing on subsequent neonatal cerebral blood flow velocity (CBFV) was studied in very preterm infants. CBFV was determined, using a pulsed Doppler technique, both in the fetal and neonatal period. Neonatally, blood pressure and transcutaneous carbon dioxide tension (TcPCO2) was monitored simultaneously; daily cranial ultrasound examinations were performed. In infants with evidence of brainsparing a higher mean value of CBFV and a different pattern of changes of CBFV during the first week of life was demonstrated compared with infants with normal fetal cerebral haemodynamics. No differences were found in blood pressure and TcPCO2. The incidence of intracranial haemorrhages and of ischaemic echo-dense lesions was also the same for both groups. In a multivariate statistical model gestational age, antepartum brainsparing, and TcPCO2 all contributed significantly in explanation of variation in CBFV. It is speculated that a different setting of cerebral autoregulation related to differences in gestational age or to brainsparing might explain the difference in changes found in neonatal CBFV.

The effectiveness of multifetal pregnancy reduction in trichorionic triplet gestation

OBJECTIVEnThe objective of the study was to assess in trichorionic triplet pregnancies the effectiveness of elective reduction to twins.nnnSTUDY DESIGNnThis was a nationwide retrospective cohort study. We compared the time to delivery and perinatal mortality in trichorionic triplet pregnancies electively reduced to twins with ongoing trichorionic triplets and primary dichorionic twins.nnnRESULTSnWe identified 86 women with reduced trichorionic triplet pregnancies, 44 with ongoing trichorionic triplets, and 824 with primary twins. Reduced triplets had a median gestational age at delivery of 36.1 weeks (interquartile range [IQR], 33.3-37.5 weeks) vs 33.3 (IQR, 28.1-35.2) weeks for ongoing triplets and 37.1 (IQR, 35.3-38.1) weeks for primary twins (P < .001). The total number of surviving children in the reduced group was 155 (90%) vs 114 (86%) in the ongoing triplet group. After reduction, 75 of women (87%) had all their fetuses surviving, compared with 36 (82%) (relative risk [RR], 1.3; 95% confidence interval [CI], 0.72-2.3) for ongoing triplets and 770 (93%) (RR, 0.91; 95% CI, 0.82-1) for primary twins. There were 6 women without any surviving children (7%) after reduction vs 5 (11.4%) (RR, 0.81; 95% CI, 0.47-1.4) among women with ongoing triplets and 32 (3.9%) (RR, 1.7; 95% CI, 0.8-3.7) in women with primary twins.nnnCONCLUSIONnIn women with a triplet pregnancy, fetal reduction increases gestational age at birth with 3 weeks as compared with ongoing triplets. However, there the impact on neonatal survival is limited.