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DOI 10.1055/s-0041-111174
Klin Padiatr 2016; 228: 69–76
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
70 Original Article
Introduction Measures
▼ Gestational age was determined using the ultrasound examina-
Spontaneous preterm premature rupture of membranes tion in the first trimester or menstrual history. PPROM was diag-
(PPROM) before 24 weeks of pregnancy, also referred to as prev- nosed when there was a history of fluid leakage, an observation
iable PPROM, occurs in less than 1 % of all pregnancies and is as- of pooling fluid from the cervical os by sterile speculum exami-
sociated with severe complications for both mother and fetus nation or presence of oligohydramnios or anhydramnios at ul-
[5, 15, 16, 24, 25, 27, 30]. Risk factors for PPROM are urogenital trasound examination. PPROM < 24 weeks of gestation was con-
infections (mostly Group B Streptococcus (GBS)), cervical cer- sidered as PPROM before viability. Oligohydramnios was consid-
clage, history of PPROM, previous preterm delivery, smoking and ered to be present when ultrasound examination did not show a
antepartum hemorrhage [2, 16, 17, 21, 27, 30]. Maternal compli- visible pocket of at least 2 cm of amniotic fluid or when the am-
cations are intra-uterine infection, retained placenta and pla- niotic fluid index was less than 5 cm. Anhydramnios was defined
cental abruption; also few cases of sepsis and maternal death as a deepest pocket of less than 1 cm [14]. When previable
have been reported [5, 7, 21, 22, 25, 26]. PPROM was diagnosed, presence of infection was assessed in
Both the gestational age at previable PPROM and at birth are pre- cervical or vaginal and urinary cultures.
dictive for the neonatal outcome [7, 29]. Common neonatal com- After having been counseled by obstetricians and neonatolo-
plications are pulmonary hypoplasia, bronchopulmonary dys- gists, parents were invited to make an informed decision for ei-
plasia (BPD), contractures and infection [16, 21, 29]. Neonatal ther active or expectant management. Active management im-
survival has improved over the last decade. However, reported plied termination of pregnancy, which in the Netherlands is le-
neonatal mortality rates remain high after this obstetric compli- gal until 24 weeks of gestation [18]. Expectant management
cation and range from 34 to 82 % [2, 22, 24–26, 28, 29]. implied bed rest, hospital admission when the fetus reached vi-
More insight into maternal, fetal and neonatal outcomes might ability and antenatal corticosteroids after 24 weeks of gestation.
improve counseling of parents and treatment decision-making. Antibiotics (amoxicillin or amoxicillin/clavulanic acid) and toco-
This can only be realized using studies with reasonably large lytic drugs (nifidipin or atosiban) were prescribed according to
samples. Waters and Mercer showed in their review that previ- the local protocol. When during expectant management signs of
ous studies had low sample sizes and were performed in multi- intra-uterine infection or fetal distress were observed, pregnan-
ple centers [27]. Furthermore previous studies showed a wide cy was terminated. The latency period was defined as the period
range in latency, morbidity and survival rates. These wide rang- between PPROM and delivery [5, 15, 27, 30]. Either vaginal or
es can be explained by different study designs, different inclu- cesarean delivery was indicated in case of intra-uterine infection;
sion criteria such as gestational age during PPROM or differences cesarean delivery in case of fetal distress. Cesarean delivery was
in local protocol regarding treatment of this special group of only performed after the fetus had reached viability.
mothers and neonates. The primary objective of the study was Neonatal resuscitation was performed by a neonatologist ac-
to investigate maternal, fetal and neonatal morbidity and mor- cording to the local protocol. Preterm and term neonates were
tality with data obtained from a large cohort in one tertiary admitted at the NICU or maternity ward.
perinatal center. Second, we determined whether time of occur-
rence of previable PPROM – before vs. after 20 weeks of preg- Outcome measures
nancy – would influence outcomes. We expected that this 20 Primary outcome was neonatal mortality after previable PPROM.
weeks’ cut-off would be most relevant to neonatal outcome Secondary outcome was morbidity of both mother and neonate
[13, 25, 28]. With these data physicians can counsel parents ap- after previable PPROM. Parameters for maternal morbidity were
propriately and together they can determine management. intra-uterine infection, sepsis, placental abruption or retained
placenta. Intra-uterine infection was defined as a maternal tem-
perature of 38 °C or higher, in combination with elevated C-reac-
Material and Methods tive protein and/or leukocyte count, the presence of leaking pu-
▼ rulent fluid from the vagina and uterine tenderness and sepsis
Study population with positive blood cultures. Placental abruption was clinically
This retrospective cohort study included all women with single- diagnosed with 2 or more of the following criteria: antepartum
ton and twin pregnancies, who presented with PPROM before 24 hemorrhage after 20 weeks of gestational age, uterine pain or
weeks of gestation at the Department of Obstetrics of the Eras- tenderness, fetal distress or death and blood clots behind the pla-
mus MC-Sophia Children’s Hospital, a tertiary perinatal center in centa [12]. The diagnosis retained placenta was made in case the
the Netherlands, between January 2002 and December 2011. placenta was not delivered within 60 min after birth. Histological
Exclusion criteria were: structural fetal abnormalities detected infection was diagnosed if examination of the placenta showed
by ultrasound examination or other prenatal testing methods. chorioamnionitis, subchorial intervillositis and/or funiculitis.
The study was approved by the medical ethics committee of Parameters for neonatal morbidity were respiratory distress
Erasmus MC, Rotterdam (MEC-2012-162). syndrome (RDS), BPD, persistent pulmonary hypertension of the
Maternal and neonatal data were extracted from the electronic neonate (PPHN), patent ductus arteriosus (PDA), infection, intra-
databases of the Department of Obstetrics and the Department ventricular hemorrhage (IVH), contractures, retinopathy of pre-
of Neonatology. Neonatal data were used from birth until dis- maturity (ROP) and necrotizing enterocolitis (NEC). RDS was diag-
charge. As in the Netherlands most neonates admitted to level III nosed on the basis of clinical and radiological signs consistent
centers are transferred to level II neonatal centers before dis- with surfactant deficiency [9]. BPD was defined as need of oxy-
charge home, additional data were collected in the centers the gen at the corrected age of 36 weeks of pregnancy [11, 19]. PPHN
neonates were transferred to. was diagnosed with clinical signs of ductal right-left shunt, with
pre- and postductal differences in saturation, and confirmed by
cardiac ultrasound [8]. PDA was diagnosed with ultrasound ex-
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
Original Article 71
Fetal and
neonatal deaths Death < 24 h
n = 116 (70.7 %) n = 31 (26.7 %)
Total fetuses
n = 164
Neonates alive
at discharge
n = 48 (29.3 %) Death > 24 h < 7 d
n = 5 (4.3 %)
Death > 7 d
n = 6 (5.2 %)
Previable
PPROM < 20 weeks
n = 10 (20.8 %)
Previable
PPROM > 20 weeks
n = 38 (79.2 %)
amination in the presence of clinical signs [23]. Infection was factant, dexamethasone, nitric oxide, RDS, BPD, PPHN, contrac-
suspected with clinical signs of infection, elevated C-reactive tures, neonatal infection, PDA, NEC, ROP and IVH. The presence
protein or leukocyte count. Sepsis was confirmed when blood of confounding, defined as a change in the regression coefficient
cultures were positive. IVH (grade 3 or higher) was diagnosed by of the central determinant of 10 %, was investigated for all poten-
cranial ultrasound [20]. Neonates were monitored for signs of tial confounders in the model in a predefined order. A sensitivity
contractures, ROP and NEC (Bell stage 2 or higher) [1, 3, 4]. analysis was performed among twin pregnancies to investigate
In addition, differences were studied between previable PPROM correlations between variables that could influence the results.
before and after 20 weeks of pregnancy. As mentioned earlier, Statistical significance was considered with 2-tailed p-values
we expected that this cut-off was most influential with neonatal of < 0.050. Data were analyzed with SPSS Statistics 20.0 (IBM
outcome (in particular neonatal survival and pulmonary hypo- Corporation, Somers, NY).
plasia) [13, 25, 28].
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
72 Original Article
Characteristic n a,b Total n a,c n a, c, d Neonatal survivors n a, c, d Fetal and neonatal P-value e
non-survivors
Age (y) f 160 32 (18.3–50.2) 164 48 30.5 (21.7–40.5) 116 32.3 (18.3–50.2) 0.078
Twin pregnancy g 160 25 (15.6 %) 164 48 3 (6.3 %) 116 26 (22.4 %) 0.014
Gravidity f 160 2 (1–16) 164 48 2 (1–10) 116 2 (1–16) 0.791
Parity f 160 1 (0–15) 164 48 1 (0–5) 116 1 (0–15) 0.826
Gestational age at PPROM (w) f 159 20.3 (12.4–23.9) 163 47 22 (12.4–23.9) 116 19 (14.0–23.7) < 0.001
< 20 weeks g 160 74 (46.3 %) 164 48 10 (20.8 %) 116 66 (56.9 %) < 0.001
Risk factors PPROM present g 160 122 (76.3 %) 164 48 36 (75.0 %) 116 90 (77.6 %) 0.721
Infection 158 64 (40.5 %) 162 48 17 (35.4 %) 114 48 (42.1 %) 0.428
GBS 157 32 (20.4 %) 161 48 9 (18.8 %) 113 23 (20.4 %) 0.816
History of PPROM 154 16 (10.4 %) 158 47 2 (4.3 %) 111 14 (12.6 %) 0.152
Antepartum hemorrhage 149 57 (38.3 %) 153 47 21 (44.7 %) 106 38 (38.0 %) 0.300
Cervical cerclage 159 19 (11.9 %) 163 48 3 (6.3 %) 115 16 (13.9 %) 0.165
Oligo- or anhydramnios g 135 110 (81.5 %) 138 46 33 (71.7 %) 92 80 (87.0 %) 0.029
Tocolytic drugs g 151 48 (31.8 %) 155 42 29 (69.0 %) 113 21 (18.6 %) < 0.001
Steroids g 150 73 (48.7 %) 153 45 45 (100 %) 108 29 (26.9 %) < 0.001
Latency period (d) f 153 10 (0–136) 159 44 53 (5–136) 115 5 (0–85) < 0.001
Gestational age at delivery (w) f 160 23.8 (15.1–36.7) 164 48 29.3 (23.9–36.7) 116 21.7 (15.1–31.3) < 0.001
Mode of delivery: vaginal g 160 134 (83.7 %) 164 48 27 (56.3 %) 116 110 (94.9 %) < 0.001
Histological evidence infection g 141 108 (76.6 %) 145 41 24 (58.5 %) 104 17 (83.7 %) 0.001
a
Number of patients the variable was obtained from; b Total number of pregnancies (n = 160); c Total number of fetuses (n = 164); d Survivors (n = 48) and non-survivors (n = 116)
were obtained from number of fetuses; e P-value is obtained from survivors vs. non-survivors; f Median (range); g Number of patients (%)
n, number; y, years; PPROM, preterm premature rupture of membranes; w, weeks; GBS, Group B Streptococcus; d, days
Characteristics n a Total n a,b Neonatal survivors n a,b Fetal and neonatal P-value c
non-survivors
Gestational age at PPROM (w) d 67 21.6 (12.4–23.9) 47 22.0 (12.4–23.9) 20 20.6 (16.4–23.7) 0.419
< 20 weeks e 67 17.0 (25.4 %) 47 9.0 (19.1 %) 20 8.0 (40.0 %) 0.073
Oligo- or Anhydramnios e 63 49.0 (77.8 %) 46 33.0 (71.1 %) 17 16.0 (94.1 %) 0.088
Latency period (d) d 62 51.5 (4–136) 44 53.0 (5–136) 18 46.0 (4–85) 0.046
Gestational age at delivery (w) d 68 28.1 (23.9–36.7) 48 29.3 (23.9–36.7) 20 26.0 (24.0–31.3) < 0.001
Gender e 0.092
Male 68 20.0 (29.4 %) 48 31.0 (64.6 %) 20 17.0 (85.0 %)
Female 68 48.0 (70.6 %) 48 17.0 (35.4 %) 20 3 (15.0 %)
Birthweight (g) d 68 1097.5 (460–2900) 48 1195.0 (600–2900) 20 775 (460–1485) 0.001
Head circumference (cm) d 50 25.0 (20.5–33.0) 39 26.0 (21.0–33.0) 11 23.0 (20.5–29.5) 0.008
Apgar score d
1 min 67 5 (0–9) 48 6 (0–9) 19 1 (1–7) 0.001
5 min 68 7 (2–10) 48 7.5 (2–10) 20 2 (2–9) 0.002
10 min 59 8 (1–10) 41 8 (4–10) 18 1 (1–9) 0.003
Resuscitation at birth e 67 32.0 (47.8 %) 48 21.0 (43.8 %) 19 11.0 (57.9 %) 0.296
a
Number of patients the variable was obtained from; b Survivors (n = 48) and non-survivors (n = 20) were obtained from number of neonates admitted at NICU (n = 67) or mater-
nity ward (n = 1); c P-value is obtained from survivors vs. non-survivors; d Median (range); e Number of patients (%); f Mean ± SD
NICU, neonatal intensive care unit; n, number; w, weeks; d, days; g, grams; cm, centimeters
tional age at delivery for pregnancies complicated by oligo- or ▶ Table 2. The overall median gestational age at de-
presented in ●
anhydramnios was 24.9 weeks (p = 0.048). Complications were livery was in this group 28.1 weeks. In neonates born after a
documented for 90 women (56.2 %); 44/160 women had an in- pregnancy complicated by oligo- or anhydramnios median
fection (27.5 %), 47/160 women had a retained placenta (29.4 %), gestational age at delivery was lower at 27.7 weeks (p < 0.030).
9/160 women had a placental abruption (5.6 %)
2 women developed sepsis and underwent a hysterectomy Previable PPROM < 20 weeks vs. > 20 weeks of
(1.3 %); one of them even developed multiple organ failure pregnancy
(0.6 %). Both women chose active management and already had Fetal and neonatal mortality is compared between previable
signs of intra-uterine infection when they presented at the hos- PPROM before and after 20 weeks of pregnancy ( ● ▶ Table 3). Of
pital. There were no maternal deaths. The incidence of maternal the 116 fetal and neonatal deaths, 77 cases (66.4 %) were origi-
complications did not differ between active and expectant man- nally expectant management cases. 28 neonates (22.4 %) died
agement (p = 0.693). within 24 h postpartum. After these first 24 h, mortality de-
A total of 68 neonates were admitted at the NICU (n = 67) or creases substantially (8.8 %). 48 neonates (38.4 %) born after ex-
maternity ward (n = 1). Characteristics of these neonates are
pectant management survived until discharge (22.7 vs. 46.9 %;
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
Original Article 73
Characteristic n b Previable PPROM < 20 n b Previable PPROM > 20 P-value c Table 4 Pregnancies characteris-
tics compared between previable
weeks weeks
PPROM before and after 20 weeks
Twin pregnancy d 76 19 (25.0 %) 88 10 (11.4 %) 0.022 of pregnancy a.
Gravidity e 76 2.5 (1–10) 88 2 (1–16) 0.894
Parity e 76 1 (0–4) 88 1 (0–15) 0.714
Gestational age at PPROM (w) e 75 17.7 (12.4–19.9) 88 22.5 (20.0–23.9) < 0.001
Risk factors PPROM d
Risk factors present 76 59 (77.6 %) 88 67 (76.1 %) 0.821
Infection 74 31 (41.9 %) 88 34 (38.6 %) 0.674
GBS 73 17 (23.3 %) 88 15 (17.0 %) 0.214
History of PPROM 72 9 (11.8 %) 86 7 (8.1 %) 0.366
Antepartum hemorrhage 73 30 (41.1 %) 80 29 (36.3 %) 0.538
Cervical cerclage 76 3 (3.9 %) 87 16 (36.3 %) 0.004
Oligo- or Anhydramnios d 60 53 (88.3 %) 78 60 (76.9 %) 0.084
Management d
Active 76 32 (42.1 %) 88 7 (8.0 %) < 0.001
Expectant 76 44 (57.9 %) 88 81 (92.0 %) < 0.001
Tocolytic drugs d 74 9 (12.2 %) 81 41 (50.6 %) < 0.001
Steroids d 72 17 (23.6 %) 81 57 (70.4 %) < 0.001
Latency period (d) e,f 43 35 (0–136) 75 12 (0–103) 0.177
Gestational age at delivery (w) e,f 44 23.1 (15.3–36.7) 81 25.3 (21.0–35.9) 0.010
Mode of delivery: vaginal d 76 65 (85.5 %) 88 72 (81.8 %) 0.523
Histological evidence infection d 69 51 (73.9 %) 76 60 (78.9 %) 0.475
a
Number of previable PPROM < 20 weeks (n = 76) and previable PPROM > 20 weeks of pregnancy (n = 88) were obtained from number
of fetuses (n = 164); b Number of patients the variable was obtained from; c P-value is obtained from previable PPROM < 20 weeks vs.
previable PPROM > 20 weeks of pregnancy; d Number of patients (%); e Median (range); f With expectant management data. Expectant
management (n = 125) was obtained from number of fetuses (n = 164)
n, number; PPROM, preterm premature rupture of membranes; w, weeks; d, days
respectively previable PPROM before and after 20 weeks). Neo- measures neonatal mortality after expectant management. Con-
nates born after previable PPROM > 20 weeks of pregnancy had a tractures and PPHN continued to be related to PPROM < 20 weeks
greater probability of being alive at discharge (p = 0.008). of pregnancy.
Differences in pregnancy characteristics between previable
PPROM < 20 weeks vs. > 20 weeks are showed in ● ▶ Table 4. More
parents opted for expectant management with previable PPROM Discussion
> 20 weeks (p < 0.001). ● ▶ Table 5 demonstrates neonatal morbid- ▼
ity and mortality and the comparison between previable PPROM This study of previable PPROM, with a relatively large study pop-
before and after 20 weeks of pregnancy. Both PPHN and contrac- ulation of 164 fetuses from one tertiary perinatal center, shows
tures are significantly more frequent with PPROM < 20 weeks that more than 50 % of the mothers develop one or more compli-
(64.7 %; p = 0.001 and 58.8 %; p < 0.001 respectively). cations (intra-uterine infection, retained placenta, placental
Factors associated with gestational age during PPROM were ex- abruption or sepsis). Neonates have a high mortality rate, espe-
amined in a multivariable analysis to control for potential con- cially neonates born after PPROM < 20 weeks of pregnancy. The
founders ( ●▶ Table 6). Because all selected participants received overall neonatal survival rate after expectant management was
antenatal steroids, this characteristic was not used in the analy- 38.4 %. In particular neonates born after PPROM < 20 weeks of
sis. Oligo- and anhydramnios were not confounding factors of pregnancy should be watched closely for PPHN and contractures.
neonatal mortality and were therefore not used in the analysis. Previous studies showed that the mother has a relatively high
Previable PPROM < 20 weeks of pregnancy is found to be an inde- incidence of intra-uterine infections (range 24.7–46.4 %), retained
pendent predictor, corrected for confounders, of the outcome placenta (> 10 %) and placental abruption (> 5 %) [5, 15, 26, 27, 29].
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
74 Original Article
In the present study, 27.5 % of women showed clinical signs of As above mentioned, the amount of remaining amniotic fluid is
intra-uterine infection, 29.4 % of retained placenta and 5.6 % of an important predictive factor for neonatal outcome [14, 28]. In
Characteristics n b Total n b Previable PPROM < 20 n b Previable PPROM > 20 P-value c
weeks weeks
Oligo- or anhydramnios d 63 49 (77.8 %) 15 14 (93.3 %) 48 35 (72.9 %) 0.156
Latency period (d) e 62 51.5 (4–136) 17 85 (51–136) 45 41 (4–103) < 0.001
Gestational age at delivery (w) e 68 28.1 (23.9–36.7) 18 29.2 (25.1–36.7) 50 27.7 (23.9–35.9) 0.101
Gender d 0.670
Male 68 20 (29.4 %) 18 12 (66.7 %) 50 36 (72.0 %)
Female 68 48 (70.6 %) 18 6 (33.3 %) 50 14 (28.0 %)
Birthweight (g) e 68 1 097.5 (460–2900) 18 1 174.5 (690–2575) 50 1 090 (460–2900) 0.483
Head circumference (cm) e 50 25 (20.5–33.0) 10 24.8 (22.7–30.2) 40 25.3 (20.5–33.0) 0.875
Resuscitation at birth d 67 32 (47.8 %) 18 7 (38.9 %) 49 25 (51.0 %) 0.378
Duration invasive ventilation (d) e 68 2.0 (0–35) 18 3 (0–13) 50 2 (0–35) 0.556
Surfactant d 65 41 (63.1 %) 17 14 (82.4 %) 48 27 (56.3 %) 0.084
Dexamethasone d 65 10 (15.4 %) 16 2 (12.5 %) 49 8 (16.3 %) 1.000
NO d 66 15 (22.7 %) 17 7 (41.2 %) 49 8 (16.3 %) 0.048
Complications d
RDS 66 39 (59.1 %) 18 12 (66.7 %) 48 27 (56.3 %) 0.443
BPD
Need of oxygen 28 days pp 65 33 (50.8 %) 18 8 (44.4 %) 47 25 (53.2 %) 0.528
Need of oxygen 36 weeks g 60 25 (41.7 %) 18 7 (38.9 %) 42 18 (42.9 %) 0.775
PPHN 66 21 (31.8 %) 17 11 (64.7 %) 49 10 (20.4 %) 0.001
Contractures 66 14 (21.2 %) 17 10 (58.8 %) 49 4 (8.2 %) < 0.001
Early infection (< 7 days pp) 67 12 (17.9 %) 17 2 (11.8 %) 50 10 (20.0 %) 0.716
Late infection (> 7 days pp) 66 28 (42.4 %) 16 4 (25.0 %) 50 24 (48.0 %) 0.105
PDA 61 15 (24.6 %) 15 2 (13.3 %) 46 13 (28.3 %) 0.317
NEC 67 4 (6.0 %) 17 0 (0.0 %) 50 4 (8.0 %) 0.565
ROP 43 7 (16.3 %) 9 0 (0.0 %) 34 7 (20.6 %) 0.314
IVH 68 5 (7.3 %) 18 0 (0.0 %) 50 5 (10.0 %) 0.315
Alive at discharge d 68 48 (70.6 %) 18 10 (55.6 %) 50 38 (76.0 %) 0.103
Duration NICU stay (d) e 68 10.5 (0–145) 18 7.5 (1–145) 50 18 (0–119) 0.130
Duration of hospitalization (d) e 63 46 (1–188) 17 30 (1–145) 46 56 (1–188) 0.135
a
Number of previable PPROM < 20 weeks (n = 18) and previable PPROM > 20 weeks (n = 50) were obtained from neonates admitted at NICU (n = 67) or maternity ward (n = 1);
b
Number of patients the variable was obtained from; c P-value is obtained from previable PPROM < 20 weeks vs. previable PPROM > 20 weeks of pregnancy; d Number of patients
(%); e Median (range); f Mean ± SD; g Need of oxygen at the corrected age of 36 weeks amenorrhea
n, number; d, days; w, weeks; g, grams; cm, centimeters; NO, nitric oxide; RDS, respiratory distress syndrome; BPD, bronchopulmonary dysplasia; pp, post-partum; PPHN,
persistent pulmonary hypertension of the neonate; PDA, patent ductus arteriosus; NEC, necrotizing enterocolitis; ROP, retinopathy of prematurity; IVH, intraventricular hemor-
rhage; NICU, neonatal intensive care unit
placental abruption. The higher percentage of retained placentas the present study oligohydramnios was mostly seen with
can be explained by the fact that previous studies described PPROM < 20 weeks of pregnancy and in neonatal non-survivors.
higher gestational ages during PPROM and neonates where Gestational age at delivery was lower in the presence of oligohy-
therefore more likely to be delivered at higher gestational ages, dramnios after expectant management and with admitted neo-
which decreases the chance of a retained placenta. nates. However, in the latter group, the presence of oligohy-
The median latency period, after expectant management, with dramnios did not exert an influence on survival.
previable PPROM < 20 weeks was significantly longer than with The overall neonatal mortality rate was 70.7 vs. 34 %–82 % in pre-
previable PPROM > 20 weeks of pregnancy (35 vs. 12 days). Pre- vious studies [15, 24, 26,
27,
29]. Most were stillborn and
vious studies show latency ranges from 62 h until 63 days deaths < 24 h postpartum. These are often related with pulmo-
[5, 7, 13, 22, 25–27, 29]. A longer latency period is proven to be a nary hypoplasia or neonatal sepsis. These deaths were particu-
predictor for pulmonary hypoplasia, which is associated with larly seen with PPROM < 20 weeks of pregnancy. The chance of
high morbidity (PPHN, chronic pulmonary hypertension, BPD) survival was 91.2 % after the first 24 h postpartum, and was
and mortality rates [28]. Nevertheless, neonatal survival is high- irrespective of time of occurrence of PPROM.
er when delivery is at a higher gestational age. Oligohydramnios The neonatal survival rate with expectant management was
due to PPROM is partly responsible for poorer fetal lung develop- 38.4 vs. 17–80 % in previous studies [5, 7, 13, 15, 22, 24, 26–28]. It
ment. During midtrimester, fetal lung development coincides was highest for neonates born after previable PPROM > 20 weeks,
with the critical canalicular stage. Therefore, pulmonary hypo- despite the fact that neonates born after PPROM < 20 weeks of
plasia is associated with gestational age at PPROM [24, 28]. The pregnancy were born at a higher gestational age. These neo-
prevalence of BPD was 41.7 vs. 13–60 % in previous studies nates’ higher risk to develop pulmonary morbidity might con-
[7, 15, 24, 25, 28, 29]. Because this study only involved previable tribute to the higher mortality rate. After adjustment for possi-
PPROM, we had expected this high prevalence of BPD. ble confounders, PPROM < 20 weeks appeared to be indepen-
dently associated with neonatal mortality.
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
Original Article 75
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
76 Original Article
Conflict of interest: The authors declare no conflict of interest. 16 Mercer BM. Preterm premature rupture of the membranes. Obstet
Gynecol 2003; 101: 178–193
17 Merenstein GB, Weisman LE. Premature rupture of the membranes:
References neonatal consequences. Semin Perinatol 1996; 20: 375–380
1 Bell MJ. Neonatal necrotizing enterocolitis. N Engl J Med 1978; 298: 18 Nederlandse Vereniging Obstetrie en Gynaecologie (NVOG). Richtlijn
281–282 zwangerschapsafbreking tot 24 weken [Dutch Society of Obstetrics
2 Blumenfeld YJ. The effect of preterm premature rupture of membranes and Gynecology. Guideline termination of pregnancy before 24 weeks
on neonatal mortality rates. Obstet Gynecol 2010; 116: 1381–1386 of gestational age] (in Dutch), approved 2005
3 Bonilla-Musoles F, Machado LE, Osborne NG. Multiple congenital con- 19 Northway WH Jr. An introduction to bronchopulmonary dysplasia.
tractures (congenital multiple arthrogryposis). J Perinat Med 2002; Clin Perinatol 1992; 19: 489–495
30: 99–104 20 Papile LA. Incidence and evolution of subependymal and intraven-
4 Darin N, Kimber E, Kroksmark AK et al. Multiple congenital contrac- tricular hemorrhage: a study of infants with birth weights less than
tures: birth prevalence, etiology, and outcome. J Pediatr 2002; 140: 1,500 gm. J Pediatr 1978; 92: 529–534
61–67 21 Parry S, Strauss JF 3rd. Premature rupture of the fetal membranes.
5 Dinsmoor MJ. Outcomes after expectant management of extremely N Engl J Med 1998; 338: 663–670
preterm premature rupture of the membranes. Am J Obstet Gynecol 22 Pristauz G, Bader AA, Schwantzer G et al. Assessment of risk factors for
2004; 190: 183–187 survival of neonates born after second-trimester PPROM. Early Hum
6 Donders AR, van der Heijden GJ, Stijnen T et al. Review: a gentle intro- Dev 2009; 85: 177–180
duction to imputation of missing values. J Clin Epidemiol 2006; 59: 23 Reese J. Patent ductus arteriosus: mechanisms and management.
1087–1091 Semin Perinatol 2012; 36: 89–91
7 Farooqi A, Holmgren PA, Engberg S et al. Survival and 2-year outcome 24 Shumway J. Impact of oligohydramnios on maternal and perinatal
with expectant management of second-trimester rupture of mem- outcomes of spontaneous premature rupture of the membranes at
branes. Obstet Gynecol 1998; 92: 895–901 18–28 weeks. J Matern Fetal Med 1999; 8: 20–23
8 Greenough A, Khetriwal B. Pulmonary hypertension in the newborn. 25 Soylu H, Jefferies A, Diambomba Y et al. Rupture of membranes before
Paediatr Respir Rev 2005; 6: 111–116 the age of viability and birth after the age of viability: comparison of
9 Halliday HL, McClure G, Reid MM et al. Controlled trial of artificial outcomes in a matched cohort study. J Perinatol 2010; 30: 645–649
surfactant to prevent respiratory distress syndrome. Lancet 1984; 1: 26 Verma U, Goharkhay N, Beydoun S. Conservative management of pre-
476–478 term premature rupture of membranes between 18 and 23 weeks
10 Janssen KJ, Donders AR, Harrell FE Jr et al. Missing covariate data in of gestation – maternal and neonatal outcome. Eur J Obstet Gynecol
medical research: to impute is better than to ignore. J Clin Epidemiol Reprod Biol 2006; 128: 119–124
2010; 63: 721–727 27 Waters TP, Mercer BM. The management of preterm premature rup-
11 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit ture of the membranes near the limit of fetal viability. Am J Obstet
Care Med 2001; 163 1723–1729 Gynecol 2009; 201: 230–240
12 Kramer MS, Usher RH, Pollack R et al. Etiologic determinants of abrup- 28 Winn HN, Chen M, Amon E et al. Neonatal pulmonary hypoplasia and
tio placentae. Obstet Gynecol 1997; 89: 221–226 perinatal mortality in patients with midtrimester rupture of amni-
13 Lindner W, Pohlandt F, Grab D et al. Acute respiratory failure and otic membranes – a critical analysis. Am J Obstet Gynecol 2000; 182:
short-term outcome after premature rupture of the membranes and 1638–1644
oligohydramnios before 20 weeks of gestation. J Pediatr 2002; 140: 29 Xiao ZH, Andre P, Lacaze-Masmonteil T et al. Outcome of premature
177–182 infants delivered after prolonged premature rupture of membranes
14 Magann EF, Sanderson M, Martin JN et al. The amniotic fluid index, before 25 weeks of gestation. Eur J Obstet Gynecol Reprod Biol 2000;
single deepest pocket, and two-diameter pocket in normal human 90: 67–71
pregnancy. Am J Obstet Gynecol 2000; 182: 1581–1588 30 Yeast JD. Preterm premature rupture of the membranes before viabil-
15 Manuck TA, Eller AG, Esplin MS et al. Outcomes of expectantly managed ity. Clin Perinatol 2001; 28: 849–860
preterm premature rupture of membranes occurring before 24 weeks
of gestation. Obstet Gynecol 2009; 114: 29–37
van der Marel I et al. Rupture of Membranes before Viability … Klin Padiatr 2016; 228: 69–76
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