Incidence and management of premature rupture of membranes in Victoria, Australia: A retrospective cohort study of 636 590 births between 2009 and 2017.

BACKGROUND: Premature rupture of membranes (PROM) is a complication affecting 7-12% of pregnancies in which fetal chorioamniotic membranes rupture before labour begins. Preterm PROM (PPROM) (ie <37 weeks gestation) precedes one-third of preterm births, exposing the fetus to increased morbidity from placental abruption, respiratory distress syndrome and sepsis. AIM: To analyse trends in the incidence and mode of birth in preterm and term PROM in Victoria, Australia between 2009 and 2017. MATERIALS AND METHODS: This retrospective population-based cohort study included all singleton pregnancies from 2009 to 2017. We examined women with PROM (both <37 weeks (PPROM) and at term). Management was assessed in three categories: (a) expectant management; (b) induction of labour (IOL); and (c) elective caesarean section (elCS). A multinomial logistic regression model was used to adjust for confounders influencing the choice of management. RESULTS: Of 636 590 singleton pregnancies, 52 669 (8.3%) births with PROM at term (42 439; 6.7%) or PPROM (10 230; 1.6%) were identified. Of these, the majority were managed expectantly (n = 22 726; 43.1%), or with IOL (25 931; 49.2%). While elCS represented only 7.6% of these cases (n = 4012), its use rose consistently from 2009 to 2017 for PROM at term and PPROM alike. For women with PPROM at 34-36 weeks the odds of elCS increased by 5% annually (adjusted odds ratio (aOR) 1.05; 95% CI 1.02-1.08) and 2% for IOL (aOR 1.02; 95% CI 1.00-1.05) vs expectant management. CONCLUSIONS: The use of elCS and IOL in PPROM is rising in Victoria, particularly between 34 and 36 completed weeks of pregnancy. Research is needed to determine the drivers for this increase.

Hypertensive disorders in pregnancy - Trends over eight years: A population-based cohort study.

OBJECTIVE: To describe the incidence and trends of hypertensive disorders of pregnancy and adverse pregnancy outcomes in recent years in Victoria, Australia. DESIGN: Retrospective population-based cohort study, 2010 to 2017. SETTING: State of Victoria, Australia. PARTICIPANTS: Population-based cohort study. MAIN OUTCOME MEASURES: Incidence of hypertensive disorders and its subtypes over time. Composite of major adverse maternal and perinatal outcome. RESULTS: The incidence of hypertensive disorders (n = 36,406/614,524 pregnancies with 624,193 births) and all its subtypes has been stable, (n = 4,192/73,235 = 5.7% in 2010 to 4,601/78,576 = 5.9% in 2017). Compared to no hypertension, hypertensive disorders were associated with medically-initiated birth (aOR 4.70 [4.56, 4.84]), caesarean section (aOR 1.46 [1.43, 1.50]), placental abruption (aOR 1.94 [1.69, 2.22]), maternal intensive care or high-dependency unit admission (aOR 6.80 [6.45, 7.17]), composite of major adverse maternal outcome (aOR 3.87 [3.70, 4.04]), and composite of major adverse perinatal outcome (aOR 1.63 [1.56, 1.70]). The worst maternal and perinatal outcomes were among women with superimposed and early preterm preeclampsia. CONCLUSION: The incidence of all hypertensive disorders in pregnancy has remained stable over time. Early-onset preeclampsia and superimposed preeclampsia were most strongly associated with adverse pregnancy outcomes.

Routine first trimester combined screening for preterm preeclampsia in Australia: A multicenter clinical implementation cohort study.

OBJECTIVE: To assess pregnancy outcomes following first trimester combined screening for preterm preeclampsia in Australia. METHODS: We compared pregnancy outcomes of women with singleton pregnancies who underwent first trimester combined preeclampsia screening with the Fetal Medicine Foundation algorithm between 2014 and 2017 in Melbourne and Sydney, Australia, with those from women who received standard care. The primary outcomes were preterm preeclampsia and screening performance. Effect estimates were presented as risk ratios with 95% confidence intervals. RESULTS: A total of 29 618 women underwent combined screening and 301 566 women received standard care. Women who had combined screening were less likely to have preeclampsia, preterm birth, small neonates, and low Apgar scores than the general population. Women with high-risk results (≥1 in 100) were more likely to develop preterm preeclampsia (2.1% vs. 0.7%, risk ratio [RR] 3.04, 95% CI 2.46-3.77), while low-risk women (risk <1 in 100) had lower rates of preterm preeclampsia (0.2% vs. 0.7%, RR 0.26, 95% CI 0.19-0.35) and other pregnancy complications. Screening detected 65.2% (95% CI 56.4-73.2%) of all preterm preeclampsia cases, with improved performance after adjustment for treatment effect. CONCLUSIONS: First trimester screening for preeclampsia in clinical practice identified a population at high risk of adverse pregnancy outcomes and low-risk women who may be suitable for less intensive antenatal care.

Serum leukotriene B4 and hydroxyeicosatetraenoic acid in the prediction of pre-eclampsia.

INTRODUCTION: Pre-eclampsia (PE) affects 2-8% of pregnancies worldwide. Despite identification of numerous possible biomarkers, accurate prediction and early diagnosis of PE remain challenging. We examined the potential of leukotriene B4 (LTB4) and 15-hydroxyeicosatetraenoic acid (15(S)-HETE) as biomarkers of PE by comparing serum levels at three gestational age (GA) groups between normotensive pregnancies and asymptomatic women who subsequently developed preterm or term-PE. METHODS: This is a case-control study drawn from a prospective study of adverse pregnancy outcomes with serum samples collected at 19-24 weeks (n = 48), 30-34 weeks (n = 101) and 35-37 weeks (n = 54) GA. LTB4 and 15(S)-HETE levels were determined by ELISA. Serum level multiples of the median (MoM) were compared between normal and PE-pregnancies. Association between LTB4 and 15(S)-HETE and GA at delivery was investigated with Cox proportional-hazards models. RESULTS: Serum LTB4 levels were lower in women of East-Asian ethnicity, higher in women with PE history, and increased with GA in normotensive pregnancies, but not in PE. LTB4 was elevated at 19-24 weeks in women who developed preterm-PE. There was a negative association between LTB4 MoM and interval between sampling and delivery with PE at 19-24 weeks only. Serum 15(S)-HETE levels were not influenced by GA at testing and were elevated in women of South-Asian ethnicity. Median 15(S)-HETE levels were unchanged in preterm and term-PE at any GA. DISCUSSION: LTB4 was higher at 19-24 weeks in pregnancies that developed preterm-PE versus unaffected pregnancies, suggesting it is a potentially useful predictive marker of preterm PE in the second trimester.

Trends in preterm birth in twin pregnancies in Victoria, Australia, 2007-2017.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality worldwide. In many countries, the preterm birth rate in women with a multiple pregnancy is increasing, mostly due to an increase in iatrogenic preterm birth. AIMS: To investigate trends in preterm birth in twin pregnancies in Victoria, Australia, in relation to maternal and perinatal complications. MATERIALS AND METHODS: We conducted a retrospective population-based cohort study in all women with a twin pregnancy who delivered at or after 20 weeks of gestation in the state of Victoria, Australia between 2007 and 2017. Annual spontaneous and iatrogenic preterm birth rates were calculated and trends analysed. Incidence of adverse pregnancy outcomes, maternal complications and risk factors for preterm birth were analysed. RESULTS: We studied 12 757 women with a twin pregnancy. Between 2007 and 2017 the preterm birth rate increased from 641/1231 (52%) to 803/1158 (69%), mainly due to an increase in iatrogenic preterm birth from 342/1231 (28%) to 567/1158 (49%). This was irrespective of the presence of pregnancy complications. Our study showed neither a decrease in perinatal mortality from 28 weeks of gestation nor in preterm average weekly prospective stillbirth risk. CONCLUSION: Preterm birth rates in twins in Victoria are increasing, mainly driven by an increase in iatrogenic preterm birth. This occurred both in complicated and non-complicated twin pregnancies, and has not been accompanied by reduction in perinatal mortality from 28 weeks.

Trends in singleton preterm birth in Victoria, 2007 to 2017: A consecutive cross-sectional study.

INTRODUCTION: Preterm birth is a major cause of perinatal morbidity and mortality worldwide. In many countries preterm birth rates are increasing, largely as a result of increases in iatrogenic preterm birth, whereas in other countries rates are stable or even declining. The objective of the study is to describe trends in singleton preterm births in Victoria from 2007 to 2017 in relation to trends in perinatal mortality to identify opportunities for improvements in clinical care. MATERIAL AND METHODS: We conducted a consecutive cross-sectional study in all women with a singleton pregnancy giving birth at ≥20 weeks of pregnancy in Victoria, Australia, between 2007 and 2017, inclusive. Rates of preterm birth and perinatal mortality were calculated and trends were analyzed in all pregnancies, in pregnancies complicated by fetal growth problems, hypertension, (pre)eclampsia or prelabor rupture of membranes (PROM), and in (low-risk) pregnancies not complicated by any of these conditions. RESULTS: There were 811 534 singleton births between 2007 and 2017. Preterm birth increased from 5.9% (4074 births) to 6.4% (4893 births; P < .001), due to an increase in iatrogenic preterm birth from 2.5% (1730 births) to 3.6% (2730 births; P < .001). Comparable trends were seen in pregnancies complicated by fetal growth problems and hypertension and in pregnancies not complicated by small for gestational age (SGA), hypertension, (pre)eclampsia or PROM (all P < .001). In pregnancies complicated by SGA, hypertension, (pre)eclampsia or PROM the perinatal mortality rate from 20 weeks of gestation fell (13 to 12 per 1000 births; P < .001). In pregnancies not complicated by SGA, hypertension, (pre)eclampsia or PROM there was no significant change in the perinatal mortality from 28 weeks and no decrease in the preterm weekly prospective stillbirth risk. CONCLUSIONS: The singleton preterm birth rate in Victoria is increasing, driven by an increase in iatrogenic preterm birth, both in pregnancies complicated by SGA and hypertension, and in pregnancies not complicated by SGA, hypertension, (pre)eclampsia or PROM. While perinatal mortality decreased in the pregnancies complicated by SGA, hypertension, (pre)eclampsia or PROM, no significant reduction in perinatal mortality from 28 weeks or in preterm weekly prospective stillbirth risk was noted in the pregnancies not complicated by any of these conditions.

Ultrasound Appearances of the Acrania-Anencephaly Sequence at 10 to 14 Weeks' Gestation.

OBJECTIVES: The acrania-anencephaly sequence is a lethal condition with a high detection rate in experienced hands after 10 weeks' gestation. However, earlier in gestation, many cases remain undetected. Different phenotypic appearances have been described and might help increase the detection rate in less experienced hands and also earlier in gestation. The purpose of this study was to assess interobserver reliability in classifying cases of the acrania-anencephaly sequence during first trimester in 6 different subtypes according to their ultrasound appearances. METHODS: This was a retrospective descriptive cohort study at 3 centers for fetal imaging. Each case was classified according to its phenotypic appearance by 2 independent operators as "bilobular," "cystic," "elongated," "irregular," "foreshortened," or "overhanging." Frequencies of each type are described, and interoperator agreement was assessed with the intraclass correlation coefficient. RESULTS: From the 88 included cases, the frequencies of the different subtypes classified as overhanging, elongated, bilobular, cystic, foreshortened, and irregular were 31%, 25%, 19%, 11%, 8%, and 6%, respectively. The interoperator reliability was good, with an intraclass correlation coefficient of 0.903 (95% confidence interval, 0.853-0.937; P < .001). CONCLUSIONS: Using different subtypes may improve the detection of the acrania-anencephaly sequence. An accurate early diagnosis could lead to timely, less traumatic, and safer management of affected pregnancies.

Ultrasound Markers in Fetal Hydronephrosis to Predict Postnatal Surgery.

PURPOSE: Parents confronted with the finding of antenatal hydronephrosis (ANH) are particularly interested in whether their baby will need postnatal surgery. The objective of this study was to predict ANH requiring surgery on the basis of the fetal anteroposterior renal pelvic diameter (APRPD) and the Society for Fetal Urology (SFU) grading system. MATERIALS AND METHODS: The medical records of 179 patients with the finding of ANH were reviewed retrospectively. ANH was graded according to the SFU grading system. Prenatal ultrasound examinations were correlated to postnatal outcome, which was divided into three groups: prenatal resolution, conservative management and surgical treatment. RESULTS: 58 (32.4 %) cases were classified as prenatal resolution, 89 (49.7 %) babies were assigned to the conservative outcome group and 32 (17.9 %) patients needed surgical repair. Postnatal surgery was best predicted in the second trimester (area under the receiver operating characteristics curve: 0.839) by an APRPD cut-off of 8.3 mm (sensitivity: 77.8 %; specificity: 85.7 %; PPV of 53.9 %, NPV of 94.7 %). The combination of the parameters "progression of SFU grade" and SFU grade 3 or 4 achieved a sensitivity of 84.4 % and a specificity of 80.3 % for the prediction of surgery. CONCLUSION: Second-trimester APRPD is a useful parameter for predicting the risk for postnatal surgery. The SFU grade should be assessed in every prenatal ultrasound examination as some further risk estimates can be made based on its dynamics over time.

Treatment of severe hypertension during pregnancy: we still do not know what the best option is.

Intracranial hemorrhage and stroke are primary causes of maternal mortality in pregnancies affected by hypertensive disorders. As such antihypertensive therapy plays a crucial role in the management of severe hypertension. However, the target level to achieve the best outcome for both - mother and fetus - is still unclear. Moreover, given the lack of well-designed randomized controlled trials with standardized key outcomes, the current choice of antihypertensive medications depends rather on clinicians' preference. Furthermore, data on long-term outcomes of offspring is not available. Therefore, there is an urgent need for randomized trials comparing different anti-hypertensive options to address efficacy and safety questions.

Cranial sonographic markers of fetal open spina bifida at 11 to 13 weeks of gestation.

OBJECTIVES: To compare the sonographic signs of spina bifida obtained on axial and sagittal views of the fetal head between 11 and 13+6 weeks of gestation. METHODS: This was a retrospective study including 27 cases of spina bifida and 1003 randomly selected controls. Indirect markers of spina bifida were evaluated on stored ultrasound images. Intracranial translucency (IT), ratio between the brainstem and the brainstem-occipital bone distance (BS/BSOB), and maxillo-occipital (MO) line were assessed on sagittal view, whereas biparietal diameter (BPD), BPD to abdominal circumference ratio (BPD/AC), and aqueduct to occipital bone (aqueduct of Sylvius [AoS]) distance were measured on the axial plane. Reference ranges were developed, and cases of spina bifida were examined in relation to the reference range. RESULTS: On the sagittal view, detection rates for IT below the fifth percentile, BS/BSOB above the 95th percentile, and an abnormal MO line were 52.3%, 96.3%, and 96.3%, respectively. On the axial view, detection rates for BPD, BPD/AC, and AoS below the fifth percentile were 66.7%, 70.4%, and 77.8%, respectively. CONCLUSION: The MO line and the BS/BSOB ratio appear to be the best indirect ultrasound markers of spina bifida and can be easily obtained during the routine first-trimester scan.

Randomised controlled trials evaluating endometrial scratching: assessment of methodological issues.

STUDY QUESTION: Do randomised controlled trials (RCTs) evaluating endometrial scratching suffer from methodological issues including insufficient trial registration, statistical errors or irreproducibility, randomisation errors or miscellaneous issues? SUMMARY ANSWER: The majority of RCTs investigating endometrial scratching have methodological issues. WHAT IS KNOWN ALREADY: A large number of small RCTs investigating the effectiveness of endometrial scratching prior to in vitro fertilisation (IVF) and intrauterine insemination (IUI)/intercourse have reported favourable findings. Subsequently, systematic reviews incorporating these RCTs yielded meta-analyses in favour of endometrial scratching. Endometrial scratching has been widely adopted by infertility specialists around the world. Recently, an international RCT including 1364 women reported no benefit from endometrial scratching before IVF. STUDY DESIGN, SIZE, DURATION: We evaluated several methodological issues of RCTs investigating the effectiveness of endometrial scratching prior to IVF and IUI/intercourse. We identified 25 RCTs for IVF and 12 RCTs for IUI/intercourse with full-text publication. PARTICIPANTS/MATERIALS, SETTING, METHODS: We assessed the RCTs on the following criteria: adequacy of trial registration, statistical issues (description of statistical methods and reproducibility of univariable statistical analysis), excessive similarity or difference in baseline characteristics that is not compatible with chance (Monte Carlo simulations and Kolmogorov-Smirnov test) and miscellaneous methodological issues. MAIN RESULTS AND THE ROLE OF CHANCE: Of 25 RCTs evaluating endometrial scratching prior to IVF, only eight (32%) had adequate trial registration. In total, 10 (40%) RCTs had issues regarding statistical methods. Nine (69%, 13 applicable) RCTs had at least one inconsistency between reported and reproduced univariable statistical analysis for categorical baseline/intermediate characteristics. Statistical results of at least one outcome were not reproducible in 14 (74%, 19 applicable) RCTs. Only two (8%) RCTs had none of the above issues. Suggested by the simulations, these RCTs did not significantly violate the null hypothesis that the baseline characteristics were the results of a properly conducted randomisation process (P = 0.4395).Of 12 IUI/intercourse RCTs, only 2 (17%) had adequate trial registration. In total, five (42%) studies had issues of statistical methods. Inconsistency between reported and reproduced univariable analysis for baseline/intermediate categorical variable(s) was found in four (57%, 7 applicable) RCTs. Statistical analysis was not reproducible for at least one outcome in eight (80%, 10 applicable) studies. All RCTs had at least one of the above issues. These RCTs were inconsistent with the null hypothesis that their baseline characteristics were the results of proper randomised allocation (P = 1.659*10-7). LIMITATIONS, REASONS FOR CAUTION: We were unable to assess RCTs which were not published as full-text papers. We could not analyse individual participant data to investigate possible reasons for statistical inconsistencies. The method to infer the likelihood of proper random sampling rests on assumptions including independent baseline characteristics, simple randomisation and no publication bias. WIDER IMPLICATIONS OF THE FINDINGS: The methodological issues common to RCTs evaluating endometrial scratching may have biased the results of the trials. Further development and validation of these novel methods may be helpful for the critical appraisal of RCTs. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought to support this work. B.W.M. is supported by a National Health Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. D.W. is supported by a grant from the Paracelsus Medical University Salzburg, Austria (PMU Research Fund-PMU FFF Number: L-18/02/006-WET) and by Drs Haackert Foundation, Germany. S.L. is an author of a trial included in this study, an author of an included systematic review and a Cochrane editor. All other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The gap between the aorta and the superior vena cava: A sonographic sign of persistent left superior vena cava and associated abnormalities.

OBJECTIVES: To assess the distance between the right superior vena cava (SVC) and the aorta in fetuses with bilateral superior vena cava as a possible sonographic marker for this. METHODS: This was a nested case-control study including 20 cases of bilateral SVC and 40 gestational age-matched controls. The distance between the right SVC and the aorta was measured at the level of the three-vessel trachea view in stored images, as well as the diameters of the aorta and the right SVC. RESULTS: The distance between the aorta and the right SVC was significantly larger in the cases of a left SVC compared with controls, P < .001. A distance of 2.0 mm or more was found in 70% of the cases and 5% of the controls, with a gestational-age adjusted area under the receiver-operating characteristics (ROC) curve for the diagnosis of left SVC of 0.93 (95% CI 0.87-0.99). The aorta and the right SVC were significantly smaller in cases compared with controls, and there was a significant association with other cardiac and extracardiac abnormalities amongst cases of persistent left SVC. CONCLUSION: An increased distance between the aorta and the right SVC is associated with the diagnosis of bilateral SVC.

Evidence-Based Prevention of Preeclampsia: Commonly Asked Questions in Clinical Practice.

In this review, we discuss the recent literature regarding the prevention of preeclampsia and aim to answer common questions that arise in the routine antenatal care of pregnant women. Prescription of low-dose aspirin for high-risk patients has been shown to reduce the risk of preeclampsia (PE). A daily dose between 100 and 150 mg taken in the evening should be initiated prior to 16 weeks of gestation and can be continued until delivery. Calcium supplementation seems to be advantageous but currently it is only considered for patients with poor dietary intake and high risk for PE. Recent data about heparin are still conflicting, and therefore, heparin can currently not be recommended in the prevention of PE.

Prenatal screening for pre-eclampsia: Frequently asked questions.

The current approach to screening for pre-eclampsia is based on guidelines that rely on medical and obstetric history in early pregnancy to select a high-risk group that might benefit from low-dose aspirin. However, combined screening tests with the addition of biophysical and biochemical measurements have shown significantly better detection rates for preterm pre-eclampsia. Furthermore, the administration of aspirin for the 10% screen-positive group can lead to a significant reduction in severe and preterm forms of pre-eclampsia. This review aims to answer frequently asked questions related to the clinical implementation of screening and the management of screening results.

Contemporary Outcomes and Factors Associated With Mortality After a Fetal or Neonatal Diagnosis of Ebstein Anomaly and Tricuspid Valve Disease.

BACKGROUND: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare anomalies and data on outcomes after a fetal or neonatal EA/TVD diagnosis are conflicting. METHODS: To examine the outcome and identify markers predictive of mortality, we reviewed our single-centre experience from 2000-2014. Variables were analyzed separately for cases diagnosed in utero without pregnancy termination and for all live-born patients. RESULTS: Of 47 fetal cases, 8 (17%) died in utero and 10 (21%) as neonates. Independent predictors associated with fetal demise included severe tricuspid regurgitation with a Doppler gradient < 40 mm Hg (odds ratio, 1.22 per mm Hg deduction; P = 0.003) and pulmonary regurgitation (odds ratio, 11.4; P = 0.03) at the baseline examination. A novel prognostic score (range, 0-10) combining the severity of 5 echocardiographic findings was independently associated with overall mortality (hazard ratio [HR], 1.39 per point increase; P = 0.01). Survival rates of 66 live births at 1 month, 1 year, and 5 years were 86%, 82%, and 80% respectively, and 75%, 60%, and 55% remained free from surgery at the same points in time. Factors associated with postnatal death in multivariate analysis included a younger gestational age at birth (HR per week, 1.59; P < 0.001), tricuspid annulus diameter (HR per z-score increase, 1.76; P = 0.004), and no pulmonary forward flow (HR, 4.63; P = 0.03). CONCLUSIONS: Our experience with fetal and neonatal EA/TVD shows better survival rates than previously reported. Mortality after a fetal diagnosis was significantly associated with hemodynamic changes indicative of a circular shunt, including pulmonary and tricuspid regurgitation severe enough to cause diastolic umbilical arterial flow reversal.

Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the literature.

Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all trisomy 13 cases. It occurs when two cell populations that are karyotypically different are present in the same individual and are derived from a single zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and longer survival, making genetic counseling a difficult task. Capillary hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases. We report on an 18-months-old girl with extensive cutaneous anomalies, mild dysmorphic features, and slight psychomotor delay, without structural defects and provide an up-to-date review of all cases of trisomy 13 mosaicism with skin involvement. To our knowledge, this is the second clinical report of a patient with trisomy 13 mosaicism with hemangiomas and port wine stains, but no structural defects. © 2015 Wiley Periodicals, Inc.

Tocolysis with the ß-2-sympathomimetic hexoprenaline increases occurrence of infantile haemangioma in preterm infants.

BACKGROUND: Infantile haemangioma (IH) is the most commonly observed tumour in children. Off-label pharmacological treatment of IH with the beta-blocker propranolol induces regression of IH. Based on the fact that IH are more frequently observed in premature babies than in mature babies and the evidence that beta-blocker therapy leads to regression of IH, the authors generated the hypothesis that the use of ß-2-sympathomimetics during pregnancy for inhibiting premature labour might increase occurrence of IH in preterm infants. METHODS: For group comparison t test, Mann-Whitney U test and Fisher's exact test were used. Logistic regression was carried out by the forward stepwise method with Wald statistics. RESULTS: Data of 328 preterm infants (<32 gestational weeks) or with a birth weight of less than 1500 g (<36 gestational weeks) born between January 2006 and December 2008 were analysed. A total of 15 were excluded due do death within the 1st month of life, 38 because of lost to follow-up and six due to incomplete data. Complete data of 269 preterm infants were retrospectively analysed. During the follow-up period of median 1.6 years, 50 infants developed one or more IH within their first 6 months of life. IH occurred in 40/181 patients with intrauterine exposure to the ß-2-sympathomimetic hexoprenaline and in 10/88 without exposure (OR=4.3; 95% CI 1.4 to 13.8). Furthermore, the influence of antenatal exposure to glucocorticosteroids for induction of lung development was analysed. Prenatally exposed subjects showed reduced occurrence of IH (OR=0.2; 95% CI 0.05 to 0.8). CONCLUSION: Intrauterine exposure to the ß-2-sympathomimetic hexoprenaline might increase the occurrence of IH in preterm infants.