Joke H. Kok

Neonatal effects of nifedipine and ritodrine for preterm labor

Objective We compared nifedipine and ritodrine for treatment of preterm labor with respect to neonatal outcome. Methods We conducted an open randomized multicenter study of neonatal outcome in 185 women who received either oral nifedipine (n = 95) or intravenous (IV) ritodrine (n = 90) for treatment of preterm labor. Secondary outcome measures included neonatal mortality and morbidity, especially neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), and intracranial bleeding. Results There were no significant differences in umbilical artery pH values and Apgar scores between groups. Nifedipine was associated with lower admission rates to the NICU (49% versus 66%; odds ratio 0.51, confidence interval 0.28, 0.93) compared with ritodrine, and lower incidences of RDS (21% versus 37%; 0.46, 0.24, 0.89), intracranial bleeding (18% versus 31%; 0.48, 0.24, 0.96), and neonatal jaundice (52% versus 67%; 0.53, 0.29, 0.97). Logistic regression analysis showed that even after correction for gestational age at birth, newborn risk of RDS, intracranial bleeding, or neonatal jaundice was significantly lower in the nifedipine group than the ritodrine group. Conclusion Nifedipine for treatment of preterm labor was associated with a lower incidence of neonatal morbidity than ritodrine. That difference appeared to be partly because of the higher tocolytic efficacy of nifedipine and partly because of an intrinsic beneficial effect of nifedipine, or the lack of harmful effects when compared with ritodrine.

Visual perception and visual-motor integration in very preterm and/or very low birth weight children: A meta-analysis

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual perceptive and visual-motor integration abilities. Very preterm born children showed deficits in visual-spatial abilities (medium to large effect sizes) but not in visual closure perception. Tests reporting broad visual perceptive indices showed inconclusive results. In addition, impaired visual-motor integration was found (medium effect size), particularly in boys compared to girls. The observed visual-spatial and visual-motor integration deficits may arise from affected occipital-parietal-frontal neural circuitries.

Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes A Randomized Controlled Trial

IMPORTANCE In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome. OBJECTIVE To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth. DESIGN, SETTING, AND PARTICIPANTS APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010). INTERVENTION Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses. MAIN OUTCOME MEASURES Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis. RESULTS Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45). CONCLUSIONS AND RELEVANCE In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time. TRIAL REGISTRATION trialregister.nl Identifier: NTR1336.

Ten-Year Follow-up of Children Born at <30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial

Background. Thyroid hormones are essential for brain development. We conducted a randomized, controlled trial with thyroxine (T4) supplementation in infants <30 weeks’ gestation and with the last neurodevelopmental follow-up moment at the age of 5.5 years. T4 supplementation was associated with improved outcome of infants <28 weeks’ gestation and worse outcome of infants of 29 weeks’ gestation. We studied gestational age–dependent effects of T4 supplementation at the mean age of 10.5 years in children participating in our randomized, controlled trial. Methods. Questionnaires regarding school outcome, behavior, quality of life, motor problems, and parental stress were sent to the parents and children and their teachers at the same time point for all surviving children (9–12 years of age). Results. Seventy-two percent of the families responded to our questionnaires. Nonrespondents had more sociodemographic risk factors and worse development until 5.5 years. At the mean age of 10.5 years, T4 supplementation was associated with better school outcome in those who were <27 weeks’ gestation and better motor outcome in those who were <28 weeks’ gestation, whereas the reverse was true for those who were born at 29 weeks’ gestation. No other gestational age–dependent outcomes were found. Conclusions. Gestation-dependent effects of T4 supplementation remain stable over time. These effects do not prove beneficial effects of T4 in infants <28 weeks but should be the background for a new randomized, controlled trial with thyroid hormone in this age group.

Hypothyroxinaemia and thyroid function after preterm birth

The concentration of thyroid hormone in preterm infants is lower than that in term infants. This phenomenon is referred to as transient hypothyroxinaemia of prematurity. Low thyroid hormone levels after very preterm birth are associated with worse developmental outcome in childhood, but only one randomized controlled trial has been carried out in the surfactant era to find out whether thyroid hormone supplementation is beneficial for developmental outcome. More studies are required to find out whether thyroid hormone supplementation is beneficial, and if so, for which preterm group.

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.

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

OBJECTIVE Our purpose was to assess the effects that fetal growth restriction exerts on the myelination of the developing brain. STUDY DESIGN Fetal 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. RESULTS At 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. CONCLUSION Accelerated 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.

Implementation of a nation-wide automated auditory brainstem response hearing screening programme in neonatal intensive care units

Aim: As part of a future national neonatal hearing screening programme in the Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate, first stage success rate, pass/referral rates, rescreening compliance, diagnostic referral rates, age of first diagnostic evaluation and prevalence of congenital hearing loss (CHL). Methods: This prospective cohort study collected data on 2513 survivors. NICU graduates with one or more risk factors according to the Joint Committee on Infant Hearing were included in a two‐stage AABR hearing screening programme. Conventional ABR was used to establish a diagnosis of CHL. Results: A total of 2513 newborns enrolled in the programme with a median gestational age of 31.6 (range 24–43) wk and a median birthweight of 1450 (range 510–4820) g. In 25 (1%) cases parents refused screening. Four out of 2513 newborns were initially lost; 2484 newborns have been tested initially. A final 98% participation rate (2465/2513) was obtained for the whole programme. After a median postmenstrual age at the first test of 33.7 (range 27–54) wk, a pass rate of 2284/2484 (92%) resulted at the first stage. The rescreening compliance after the first test was 92% (184/200). A referral rate for diagnostic ABR of 3.1% (77/2484) resulted. Of the 77 referrals 14 (18.2%) had normal screening thresholds, 15 (19.5%) had unilateral CHL and 48 (62.3%) had bilateral CHL. The prevalence of unilateral CHL was 0.6% (15/2484) and of bilateral CHL 1.9% (48/2484).

Perinatal risk factors for neurocognitive impairments in preschool children born very preterm

Aim  This study aimed to compare a broad array of neurocognitive functions (processing speed, aspects of attention, executive functioning, visual–motor coordination, and both face and emotion recognition) in very preterm and term‐born children and to identify perinatal risk factors for neurocognitive dysfunctions.

Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children

Aim  This study investigated prediction of separate cognitive abilities at the age of 5 years by cognitive development at the ages of both 2 and 3 years, and the agreement between these measurements, in very preterm children.