Accepted Article

DR. ATSUSHI NAKAYAMA (Orcid ID : 0000-0001-7513-1767)

Article type : Original Articles

Title

The prognostic factors of hydrops fetalis with pleural effusion.

Running title

The prognostic factors of hydrops fetalis.

Category of manuscripts

original articles

Authors

The corresponding author

Full name Atsushi Nakayama, MD

Postal address 3-35 Michishita-cho Nakamura-ku, Nagoya, 453-8511, Japan

Fax number +81 52 482 7733

Telephone number +81 52 481 5111

e-mail a-nakayama@nagoya-1st.jrc.or.jp

Co-author1

Full name Makoto Oshiro, MD

This article has been accepted for publication and undergone full peer review but has
not been through the copyediting, typesetting, pagination and proofreading process,
which may lead to differences between this version and the Version of Record. Please
cite this article as doi: 10.1111/ped.13357
This article is protected by copyright. All rights reserved.
Accepted Article
Department Department of Pediatrics

Institution Japanese Red Cross Nagoya Daiichi Hospital

.Co-author2

Full name Yasumasa Yamada, MD, PhD

Department Division of Reproductive and Perinatal Medical Center

Institute Aichi Medical University Hospital

Co-author3

Full name Tetsuo Hattori, MD, PhD

Department Department of Neonatology

Institution Anjo Kosei Hospital

Co-author4

Full name Yasuhiro Wakano, MD

Department1 Department of Pediatrics

Institution1 Ichinomiya municipal hospital

Department2 Department of Pediatrics and Neonatology

Institution2 Nagoya City University Graduate School of Medical Sciences

Co-author5

Full name Seiji Hayashi, MD

Department Department of Pediatrics

Institution Okazaki City Hospital

This article is protected by copyright. All rights reserved.

Accepted Article
Co-author6

Full name Minoru Kokubo, MD, PhD

Department Department of Pediatrics

Institution Aichi Prefectural Welfare Federation of Agricultural Cooperatives

Kainan Hospital

Co-author7

Full name Koji Takemoto, MD, PhD

Department Department of Pediatrics

Institution Konan Kosei Hospital

Co-author8

Full name Shigeru Honda, MD

Department Department of Pediatrics

Institution Komaki City Hospital

Co-author9

Full name Kuniko Ieda, MD

Department Department of Pediatrics

Institution Tosei General Hospital

Co-author10

Full name Hikaru Yamamoto, MD

Department Department of Neonatology

Institution Toyota Memorial Hospital,

This article is protected by copyright. All rights reserved.

Accepted Article
Co-author11

Full name Masanori Kouwaki, MD, PhD

Department Department of Pediatrics

Institution Toyohashi Municipal Hospital

Co-author12

Full name Kyoko Yokoi, MD, PhD

Department Department of Pediatrics

Institution Nagoya City West Medical Center

Co-author13

Full name Osamu Shinohara, MD

Department Department of Pediatrics

Institution Handa City Hospital

Co-author14

Full name Takenori Kato, MD, PhD

Department Department of Neonatology and Pediatrics

Institution Nagoya City University Graduate School of Medical Sciences

Co-author15

Full name Masafumi Miyata, MD, PhD

Department Department of Pediatrics

Institute Fujita Health University School of Medicine

Co-author16

This article is protected by copyright. All rights reserved.

Accepted Article
Full name Taihei Tanaka, MD

Department Department of Pediatrics

Institution Japanese Red Cross Nagoya Daini Hospital

Co-author17

Full name Masahiro Hayakawa, MD, PhD

Department Division of Neonatology, Center for Maternal-Neonatal Care

Institution Nagoya University Hospital

Conflict of Interest

The authors declare no conflict of interest.”

Abstract

Background：Hydrops fetalis (HF) has low survival rate, particularly in cases of

preterm birth. In addition, the severity index of HF has not been fully investigated yet.

This study was aimed to clarify the prognostic factors of HF patients with pleural

effusion.

Methods：All live-born HF patients with pleural effusion, except for chromosomal

abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi

Prefecture in Japan were included. The prenatal, perinatal, and postnatal information

was obtained from their medical records and was retrospectively analyzed.

Results：Forty-one HF patients with pleural effusion were included, and twenty-eight

patients (68%) survived. The multivariate logistic stepwise analysis revealed that the

gestational birth week (OR 0.71, 95% CI 0.52–0.96, p = 0.027) and standard deviation

(SD) score of the birth weight (OR 1.74, 95% CI 1.01–2.99, p = 0.045) were significant

This article is protected by copyright. All rights reserved.

Accepted Article
factors for postnatal death. All patients with both >32 gestational weeks and <3.0 birth

weight SD score survived.

Conclusions：Combined with the gestational weeks data, the birth weight SD score may

be useful to estimate the prognosis of HF patients with pleural effusion.

Keywords: hydrops fetalis, pleural effusion, preterm infant

Introduction

Hydrops fetalis (HF) is a serious disease which is defined as an abnormal fluid

collection in two or more areas of the fetal body, such as skin edema, pleural effusion,

ascites, and pericardial effusion. It presents with various etiologies, such as,

cardiovascular, hematologic, chromosomal, syndromic, inborn errors of metabolism,

infections.[1] Its prognosis is very poor, and the survival rate was reported to be

27%–48%.[2–4]

Pleural effusion is a representative symptom of HF. The origin of pleural

effusion includes heart failure due to congenital heart disease or fetal arrhythmia,

massive hemangioma, chylothorax, and lymphatic vessel hypoplasia.[4] However,

wherever the pleural effusion comes from, excessive pleural effusion may cause lung

hypoplasia or respiratory and circulatory diseases after birth. These are associated with

a poor prognosis, and need to be resolved to treat underlying diseases.

The prognostic factor of HF was reported as preterm birth, primary untreatable

disease.[3, 6-8] Several studies reported that a preterm birth might be associated with a

poor prognosis, but sometimes clinicians have to consider a preterm delivery out of

necessity because of the progression of HF or fetal distress. In that case, it is important

for clinicians to take into consideration both the immaturity and severity of HF.

This article is protected by copyright. All rights reserved.

Accepted Article
However, it is unclear to what extent prematurity may influence the prognosis as well as

the HF index of severity, for example such as edema.

The objective of this study was to investigate the prognostic factors and the severity

index of HF patients with pleural effusion. In particular, we estimate the prognosis of

preterm HF patients and the usefulness of the birth weight standard deviation (SD) score

as a severity index.

Subjects and Methods

The Aichi Prefecture is located in central Japan. It has a population of approximately

7.5 million, and there are approximately 70,000 births annually. There are 18

maternal-neonatal care centers in the area, and all complicated cases of pregnant women,

fetuses, and newborns, including HF, are managed in those facilities. We studied HF

fetuses and newborn patients who were managed in Aichi over a 5-year period (January

2009 to December 2013). HF was defined as an abnormal fluid collection in two or

more areas of the fetal or newborn body, such as skin edema, pleural effusion, ascites,

and pericardial effusion. In this study we included live-born HF patients with pleural

effusion and excluded stillbirths and those who had chromosomal abnormalities or

complicated congenital heart diseases because they were considered to directly

influence death.

Prenatal data included gestational week at the HF diagnosis, fetal therapy,

pregnancy-induced hypertension (PIH), premature rupture of the membrane (PROM),

threatened premature labor (TPL), polyhydramnios, and Mirror syndrome. Perinatal

data included gestational age, weight, height, head circumference SD score at birth, sex,

mode of delivery, cord blood pH, and Apgar score. Postnatal data included intubation,

noradrenalin, cardiopulmonary resuscitation, inhaled nitric oxygen gas, thoracocentesis,

This article is protected by copyright. All rights reserved.

Accepted Article
surfactant therapy for 72 hours after the birth, and the primary disease of HF from the

medical records, examined retrospectively. Fetal therapy was defined as fetal

thoracentesis and/or fetal thoraco-amniotic shunting. PIH was defined as maternal

hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure > 90

mmHg) at the gestational week of twenty or later. TPL was defined as tocolysis

performed at maternal admission. Polyhydramnios was defined as an observed amniotic

pocket >8 cm or an amniotic fluid index (AFI) of >24 cm by fetal ultrasonography.

Mirror syndrome was defined as a maternal edematous change, such as hypertension,

excessive weight gain over a short time, lung edema, cardiac enlargement,

hypoproteinemia, placental edema, as well as skin edema. The gestational week was

decided based on the last menstruation and was confirmed by ultrasonography at an

early gestation. The weight, height, and head circumference SD score was calculated

based on the Japanese physical standard calculation software, which was based on

143,300 healthy Japanese newborns in 2010 (http://jspe.umin.jp/medical/keisan.html

taikakubirthlongcrossv1.xlsx).

In the analysis of survival-related factors, all included cases were divided into a

survival group or a deceased group, and a univariate analysis of prenatal, perinatal, and

postnatal data compared the results between the two groups. For the significant factors,

a multivariate logistic regression analysis was performed to detect independent factors

for death, and an odds ratio was calculated. To collect information on premature HF

patient survival, we calculated the sensitivity and specificity for death according to the

gestational week and the cut-off gestational week at death. The optimal cutoff values

were defined as the point at which the value of Youden-Index (sensitivity + specificity

-1) reached the maximum value.

This article is protected by copyright. All rights reserved.

Accepted Article
All statistical analysis used EZR statistical software (v.1.31).[9] A Mann-Whitney U

test and Fisher’s exact test were used for the univariate analysis, and a logistic

regression analysis (stepwise) was used for the multivariate analysis. Correlation

coefficients were calculated by Pearson’s product-moment correlation. All statistical

analyses were assumed significant when p < 0.05.

This study was approved by the ethical committee of Japanese Red Cross Nagoya

Daiichi Hospital.

Results

A total of 87 HF patients were reported from the 18 maternal-neonatal centers over a

5-year period (2009–2013).

According to the demographic data of the Aichi prefecture, the total delivery number

was 350,497 over the same 5-year period; therefore, the incidence of HF was calculated

as 1/4028 deliveries. A total of 65 of the 87 HF patients had pleural effusion. We

excluded 24 cases because of stillbirth (n = 19), trisomy 21 (n = 3), Ebstein

malformation (n = 1), and hypoplastic left heart syndrome (n = 1); therefore, a total of

41 cases were included in this study (Fig. 1). The primary disease of HF was idiopathic

chylothorax (n = 25), lung/thoracic disease (n = 2), arrhythmia (n = 2), tumor (n = 1),

renal disease (n = 1), abdominal disease (n = 1), lymphatic vessel dysplasia (n = 1), and

unknown (n = 8). A total of 28 patients (68%) survived and 13 died (32%).

The univariate comparisons of prenatal and perinatal data between the survival and

dead groups revealed that the HF diagnosis was made earlier (26 weeks vs 30 weeks, p

= 0.004), and PROM was seen more frequently in the dead group (23% vs 0%, p =

0.029) than in the survival group (Table 1). The gestational week was earlier (30.7

weeks vs 33.8 weeks, p = 0.003), the birth weight SD score was higher (3.7 vs 2.1, p =

This article is protected by copyright. All rights reserved.

Accepted Article
0.003), a lower Apgar score was more frequently observed at 1 min < 4 (92% vs 57% p

= 0.033) and at 5 min < 6 (92% vs 50% p = 0.014) in the non-survival group compared

with those in the survival group (Table 1). The univariate comparisons of postnatal data

showed that an inhaled nitric oxide (NO) gas treatment was applied more frequently in

the dead group than in the survival group (Table 1). The stepwise multivariate logistic

analysis of seven factors that were significant in the univariate analysis revealed that the

gestational birth week (OR 0.71, 95% CI 0.52–0.96, p = 0.027) and the birth weight SD

score (OR 1.74, 95% CI 1.01–2.99, p = 0.045) were independent factors related to

postnatal death. The cutoff values obtained from the maximum area under the curve

(AUC) for the receiver ROC curves were 31.4 weeks (AUC 0.793, 95% CI 0.635-0.95)

for the gestational week and 2.8 (AUC 0.794, 95% CI 0.635-0.953) for the birth weight

SD score.

Table 2 shows the sensitivity, specificity, Youden-Index, positive predictive value

(PPV), and negative predictive value (NPV) for death after birth according to the

gestational week and birthweight SD score. In terms of the gestational week, the

sensitivity and specificity of death in patients at <32 gestational weeks was 0.77 and

0.79, respectively. The cut-off week of delivery was thought to be optimal at 32 weeks.

As for the birthweight SD score, the sensitivity and specificity of death in patients at >

3.0 SD was similar to that of > 3.5 SD. Considering a screening tool for death, a

birthweight SD score > 3.0 SD was more optimal because the sensitivity was higher

than that at > 3.5 SD.

The survival rate of HF patients with pleural effusion according to both the

gestational week and birthweight SD score was 25% for < 32 weeks and > 3.0 SD, 50%

for < 32 weeks and < 3.0 SD, 63% for > 32 weeks and > 3.0 SD, and 100% for > 32

weeks and < 3.0 SD, respectively (Fig. 2). Patients with a birthweight SD score > 3.0

This article is protected by copyright. All rights reserved.

Accepted Article
SD had larger height and head circumference SD scores and had lower Apgar scores

than those with < 3.0 SD. Although insignificant, cardiopulmonary resuscitation,

adrenalin, surfactant, and inhaled NO gas tended to be applied more frequently in > 3.0

SD group (Table 3). The birth weight SD score might show not only the degree of

edema but also the clinical severity of HF patients with pleural effusion.

Discussion

HF is a disease with a poor prognosis, and the survival rate of HF patients with

pleural effusion was reported to be from 47% to 57%.[10, 11] In this report, the survival

rate of HF infants was 68%, but the overall survival rate was 63% when chromosomal

abnormality and congenital complex heart diseases were included.

Some studies have reported that prematurity was a poor prognostic factor of HF,

although these studies were not particularly focused on HF with pleural effusion. Huang

et al.[8] reported that premature HF infants born at less than 34 gestational weeks

showed a poor prognosis with 28 live-born non-immune HF infants. Picone et al.[11]

reported that preterm birth was one of the most significant causes of a poor prognosis of

HF infants with pleural effusion. Similar to the previous studies, the gestational week

was an independent factor related to death after birth in this study. The mortality rate

was significantly lower at >32 gestational weeks (12%) than at < 32 gestational weeks

(62%). This showed that preterm HF infants survived in this cohort more than they used

to. The Society for Maternal Fetal Medicine reported that the preterm delivery of HF

fetuses should not be recommended except for maternal reasons.[7] However, if the

fetal edema or heart dysfunction deteriorates in mid or late pregnancy, parents and

medical staff must decide whether to proceed with delivery. This information might be

useful for those cases.

This article is protected by copyright. All rights reserved.

Accepted Article
In this study, we showed that the birthweight SD score was a significant prognostic

factor and that the mortality rate of patients with a birthweight SD score of > 3.0 was

4.7 times higher than those with a score of < 3.0 SD. We experienced difficulties in the

management of more edematous HF infants, although the birthweight SD score has

never been reported as an index of HF severity. The reason for this is unclear, but we

speculate that the HF mortality rate reported in previous studies was so high that no

differences would be observed according to the birthweight SD score. In this study, we

excluded HF patients with chromosomal abnormalities and/or complex congenital heart

disease, and the mortality rate was 32% in this cohort. This, as well as the recent HF

management progression, might result in the survival rate becoming relatively higher,

which resulted in clarifying the direct index that could be used to evaluate the severity

of HF with fetal pleural effusion.

The strength of the current study is that it is multi-centered and population-based.

This enabled us to examine patients with a range of HF severity. This study was

conducted during a short period; therefore, changes in the medical environment were

relatively small. We had some limitations. Firstly, this was a retrospective study. Little

has been written about the degree of skin edema, and the judgement whether skin edema

existed might be different between facilities. We also did not unify case management;

therefore, the management of mothers or infants might be different between cases or

facilities.

In addition, because the SD scores of the physical constitutions used in this study

were based on healthy Japanese infants, we cannot generalize the results to other races.

In addition, it was unclear how to estimate the birth weight SD score of each HF infant

during the fetal period. In our cohort, the fetal body weight SD score, which was

calculated by fetal ultrasonography within two days of delivery, showed a significant

This article is protected by copyright. All rights reserved.

Accepted Article
correlation with the birth weight SD score (r = 0.684, 95% CI 0.403–0.847, p < 0.001),

although this also could not be generalized. However, we can easily realize that

excessive fluid collection may be harmful regardless of race; therefore, we should pay

attention to the progression of edema as well as maturity when managing HF fetuses.

Furthermore, we could not fully evaluate the fetal therapy. The fetal therapy for pleural

effusion, such as fetal thoracocentesis or thoraco-amniotic shunting, was reported to be

beneficial for increasing the survival rate of HF fetuses.[12, 13] In this cohort, twelve

fetuses received those fetal therapies, but we found no significant differences in the

survival rate between those who received and those who did not receive fetal therapy

(75% vs 66%, p = 0.72). In a future study, HF patient management should be evaluated

by a larger prospective study that includes fetal therapy.

Conclusions

The gestational week and birth weight SD score were significantly correlated with the

prognosis of HF patients with pleural effusion. In this study, all patients who were born

at more than thirty-two gestational weeks and whose birth weight SD score was less

than 3.0 survived. These factors may become a useful index when considering whether

to deliver HF fetuses prematurely.

Disclosure

conflict of interest: The authors declare no conflict of interest.

Author contribution

N.A. O.M. T.T. and H.M. designed the study; Y.Y. H.T. W.Y. H.S. K.M. T.K. H.S. I.K.

Y.H. K.M. Y.K. S.O. K.T. M.M. and T.T. collected data; N.A. analysed data and wrote

This article is protected by copyright. All rights reserved.

Accepted Article
the manuscript; O.M. H.M. advised statistical analysis. All authors read and approved

the final manuscript.

References

1 Bellini C, Hennekam RC, Fulcheri E et al. Etiology of nonimmune hydrops

fetalis: a systematic review. Am J Med Genet A 2009;149A:844–51.

2 Sohan K, Carroll SG, De La Fuente S, Soothill P, Kyle P. Analysis of outcome in

hydrops fetalis in relation to gestational age at diagnosis, cause and treatment.

Acta Obstet Gynecol Scand 2001;80:726–30

3 Ismail KM, Martin WL, Ghosh S, Whittle MJ, Kilby MD. Etiology and outcome

of hydrops fetalis. J Matern Fetal Med 2001;10:175–81.

4 Santo S, Mansour S, Thilaganathan B et al. Prenatal diagnosis of non-immune

hydrops fetalis: what do we tell the parents? Prenat Diagn 2011;31:186–95.

5 Rocha G, Fernandes P, Rocha P, Quintas C, Martins T, Proença E. Pleural effusions

in the neonate. Acta Paediatr 2006;95:791–8.

6 Castillo RA, Devoe LD, Hadi HA, Martin S, Geist D. Nonimmune hydrops

fetalis: clinical experience and factors related to a poor outcome. Am J Obstet

Gynecol 1986;155:812–6.

7 Society for Maternal-Fetal Medicine (SMFM), Norton ME, Chauhan SP, Dashe

JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7:

nonimmune hydrops fetalis. Am J Obstet Gynecol 2015;212:127–39.

8 Huang HR, Tsay PK, Chiang MC, Lien R, Chou YH. Prognostic factors and

clinical features in liveborn neonates with hydrops fetalis. Am J Perinatol

2007;24:33–8.

9 Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for

This article is protected by copyright. All rights reserved.

Accepted Article
medical statistics. Bone Marrow Transplant 2013;48:452–8.

10 Pellegrinelli JM, Kohler A, Kohler M, Weingertner AS, Favre R. Prenatal

management and thoracoamniotic shunting in primary fetal pleural effusions: a

single centre experience. Prenat Diagn 2012;32:467–71.

11 Picone O, Benachi A, Mandelbrot L, Ruano R, Dumez Y, Dommergues M.

Thoracoamniotic shunting for fetal pleural effusions with hydrops. Am J Obstet

Gynecol 2004;191:2047–50.

12 Yinon Y, Grisaru-Granovsky S, Chaddha V, Windrim R, Seaward PG, Kelly EN et

al. Perinatal outcome following fetal chest shunt insertion for pleural effusion.

Ultrasound Obstet Gynecol 2010;36:58–64.

13 Rustico MA, Lanna M, Coviello D, Smoleniec J, Nicolini U. Fetal pleural

effusion. Prenat Diagn 2007;27:793.

Figure legends

Figure.1 Participants in this study

Eighty-seven patients participated; 46 were excluded because of no pleural effusion,

stillbirth/miscarriage, trisomy21, hypoplastic left heart syndrome, and Ebstein

malformation. Forty-one patients were included.

Figure2. Prognosis of patients plotted by gestational weeks and birth weight SD score

All patients with >32 gestational weeks at birth and birth weight SD score <3.0 survived.

Open circles indicate survivors (n = 13); triangles indicate non-survivors (n = 28).

This article is protected by copyright. All rights reserved.

Accepted Article
Table1. Prenatal, perinatal and postnatal characteristics of survivors and non-survivors

in hydrops fetalis.

Survivors Non-survivors
p
(n=28) (n=13)

GA of HF diagnosis (weeks) 30 (27-33) 26 (25-27) 0.004

HF diagnosis to delivery (weeks) 2 (1-5.5) 3 (2-5) 0.555

fetal therapy 32% 24% 0.719

PIH 4% 17% 0.209

threatened premature labor 54% 46% 0.744

PROM 0% 23% 0.029

polyhydramnios 52% 69% 0.333

Mirror syndrome 0% 8% 0.325

caesarean section 93% 85% 0.579

emergent caesarean section 15/26 (58%) 11/13 (82%) 0.262

GA at birth 33.8 (32.0-34.8) 30.7 (27.9-31.4) 0.003

BW 2,528 (2,146-3,114) 2,224 (1,460-2,530) 0.202

BW SD score 2.1 (0.9-2.9) 3.7(2.8-5.2) 0.003

sex (male) 39% 31% 0.734

Apgar score (1min) <4 57% 92% 0.033

Apgar score (5min) <6 50% 92% 0.014

umbilical cord blood pH<7.25 12% 17% 0.643

intubation 96% 100% >0.999

cardiopulmonary resuscitation 25% 46% 0.280

This article is protected by copyright. All rights reserved.

Accepted Article
adrenalin 18% 38% 0.241

surfactant 64% 92% 0.127

inhaled nitric oxide gas 25% 69% 0.014

thoracocentesis 71% 85% 0.458

abdominocentesis 11% 0% 0.539

GA; gestational weeks, HF; hydrops fetalis, PIH; pregnancy induced hypertension,

PROM; preterm rupture of membrane

Data presented as median (IQR) or (%)

Table2. Sensitivity, specificity, Youden-Index, PPV, NPV of each GA and SD score of

BW for death.

This article is protected by copyright. All rights reserved.

Accepted Article
sensitivity specificity Youden-Index PPV NPV

GA (n)

< 30 (8) 0.38 0.89 0.27 0.63 0.76

< 31 (11) 0.54 0.86 0.40 0.64 0.80

< 32 (16) 0.77 0.79 0.56 0.63 0.88

< 33 (18) 0.77 0.71 0.48 0.56 0.87

< 34 (25) 0.77 0.46 0.23 0.40 0.81

SD score of BW (n)

2.5 < (21) 0.77 0.61 0.38 0.48 0.85

3.0 < (16) 0.69 0.75 0.44 0.56 0.84

3.5 < (13) 0.62 0.82 0.44 0.62 0.82

4.0 < (8) 0.46 0.93 0.39 0.75 0.79

GA; gestational weeks, BW: birth weight, PPV; positive predictive value, NPV;

negative predictive value, Youden-Index means “sensitivity – (1- specificity)”

This article is protected by copyright. All rights reserved.

Accepted Article
Table3. Prenatal, perinatal and postnatal characteristics of patients with hydrops fetalis

according to BW SD score

BW SD score < 3 BW SD score > 3

p
(n=25) (n=16)

GA of HF diagnosis (weeks) 29 (27-31.5) 27 (25.8-29.5) 0.250

fetal therapy 32% 25% 0.739

GA at birth 33.6 (31.4-34.7) 31.5 (29.2-34.0) 0.100

2,200 2,540

BW (1,936-2,782) (2,301-3,120) 0.177

1.5 (0.4-2.3)-0.4 4.0 (3.5-5.3)1.2 <0.001

SD score of BW (-1.2-0.6) (0.1-1.2) 0.010

SD score of birth HC 1.0 (0.5-2.2) 2.8 (2.1-3.4) <0.001

Apgar score (1min) < 4 52% 94% 0.006

Apgar score (5min) < 6 52% 81% 0.097

umbilical cord blood pH < 7.25 9% 19% 0.632

intubation 96% 100% <>0.999

This article is protected by copyright. All rights reserved.

Accepted Article
cardiopulmonary resuscitation 24% 44% 0.302

adrenalin 20% 31% 0.472

surfactant 64% 88% 0.152

inhaled nitric oxide gas 28% 56% 0.104

thoracocentesis 68% 88% 0.265

abdominocentesis 12% 0% 0.268

survival 88% 44% 0.014

GA; gestational weeks, HF; hydrops fetalis, BW; birth weight, HC; head circumference

Data presented as median (IQR) or (%)

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.